Atlas of Genetics and Cytogenetics in Oncology and Haematology

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BMP4 (bone morphogenetic protein 4)

Identity

Other namesBMP2B
BMP2B1
MCOPS6
OFC11
ZYME
HGNC (Hugo) BMP4
LocusID (NCBI) 652
Location 14q22.2
Location_base_pair Starts at 54416455 and ends at 54423554 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order Genes flanking BMP4 at 14q22.2 are (centromeric to telomeric): MIR5580 (microRNA 5580), BMP4, ATP5C1P1 (ATP synthase, H+ transporting, mitochondrial F1 complex, gamma polypeptide 1 pseudogene 1).

DNA/RNA

Description Gene spans approximately 9 kbp on the minus strand at 14q22.2.
Transcription Alternative splicing in the 5'UTR gives rise to 3 transcript variants, all encoding an identical protein. Transcript variant 1 is 1917 bp in length with 4 exons (2 coding exons), transcript variant 2 is 1708 bp in length with 4 exons (2 coding exons), and transcript variant 3 is 1705 bp in length with 3 exons (2 coding exons).
In Xenopus embryos, BMP4 itself, along with the homeobox genes Vox, X-vent1, X-vent2, GATA-1, GATA-2 and AP-1 were found to induce the expression of BMP4 and control dorsoventral patterning in the mesoderm (Jones et al., 1992; Kim et al., 1998; Onichtchouk et al., 1996; Schmidt et al., 1996), whereas organizer signals, chordin and noggin, and X-lim1 negatively regulate BMP4 transcription (Kim et al., 1998). Lung specification in Xenopus depends on the suppression of BMP4 expression by zinc-finger transcriptional repressors Osr1 and Osr2 (Rankin et al., 2012).
Analysis of the mouse BMP4 gene identified 2 G-C rich Sp1 binding motifs proximal to the transcriptional start sites for exons I and II (Kurihara et al., 1993). The presence of dual promoter regions flanking exons I and II were later confirmed in human cancer cell lines (van den Wijngaard et al., 1996). Mouse BMP4 is negatively regulated by direct binding of chicken ovalbumin upstream-transcription factor I (COUP-TF1) to the proximal promoter of exon I (Feng et al., 1995). Deletion analysis of the mouse BMP4 promoter in MC3T3E1 cells identified a cis-acting E-box element proximal to the transcriptional start site that is bound by upstream regulatory factor (USF), a member of the helix-loop-helix family of regulatory proteins (Ebara et al., 1997). In mouse development, GATA-4 and -GATA-6 were found to specifically regulate BMP4 transcription to mediate endoderm-mesoderm signalling and early vasculogenesis (Nemer et al., 2003). Similarly, analysis of mouse embryonic stem cells identified the transcriptional corepressor Bcor as an important regulator of ES cell differentiation into mesoderm, ectoderm and hematopoietic lineages through regulating developmental genes including BMP4 expression (Wamstad et al., 2008). Furthermore, the transcription factor Cdx2 has been shown to directly regulate BMP4 expression in mouse trophoblast cells to promote early mouse embryogenesis (Murohashi et al., 2010), while Shox2 regulates BMP4 expression to promote pacemaker development in the murine heart (Puskaric et al., 2010).
Analysis of the human BMP4 promoter in U2OS and SaOS2 cells identified the lack of a proximal TATA box, while sharing similar transcriptional start sites and regulatory elements with the mouse BMP4 promoter (Helvering et al., 2000; Shore et al., 1998). Putative binding motifs for AP1, Sp1, CRE, Cfab1 were identified, and direct binding of Cfab1 to the BMP4 promoter was confirmed, along with transcriptional upregulation of BMP4 by osteogenic compounds such as retinoic acid and the phorbol ester PMA (Helvering et al., 2000).
Transcriptional control of BMP4 is also important in diseased states. During recovery from acute anemia, hypoxia induces BMP4 expression and subsequent erythropoiesis in the murine spleen through direct binding of HIF2alpha to the BMP4 promoter (Wu et al., 2010). In retinal pigment epithelium cells of patients suffering from the wet form, but not the dry form, of macular degeneration, TNFalpha represses BMP4 transcription through phosphorylation of the transcription factor Sp1, demonstrating a BMP4 expression-dependent molecular switch (Xu et al., 2011). In hepatocellular carcinoma cells, Ets-1 was demonstrated to directly regulate hypoxia-induced BMP4 transcription to promote tumorigenesis (Maegdefrau et al., 2009). In colorectal cancer cells, oncogenic KRAS can repress BMP4 expression through a novel ras-responsive region (Duerr et al., 2012).
In addition to many proximal regulatory sites, the BMP4 gene, along with many other BMP family genes, resides within a conserved gene desert, which contains many additional distal cis-regulatory regions (located over 30 kbp from coding sequences) that control BMP4 expression in a spatiotemporal and tissue-dependent manner (Chandler et al., 2009; Pregizer et al., 2009). For example, an evolutionarily conserved distal enhancer site, 46 kb upstream of the transcriptional start site, is bound by Pitx2 and likely participates in tooth and limb morphogenesis (Jumlongras et al., 2012). Furthermore, a common polymorphism found within the distal BMP4 promoter (17kb upstream) acts as a cis-acting enhancer of BMP4 transcription, and is significantly associated with colorectal cancer risk (Lubbe et al., 2012).
Pseudogene None annotated.

Protein

Description BMP4, a member of the TGFbeta superfamily of signalling molecules, is a 46.5 kDa, 408 aa protein that is translated as a precursor containing a signal peptide (aa 1 - 19), a prodomain (aa 20 - 292) and a mature domain (aa 293 - 408). After the BMP signal peptide has been removed, dimerization of the proproteins proceeds. Proprotein cleavage is achieved by the candidate serine endoproteases Furin, PCSK5, PCSK6, or PCSK7 at the consensus sequence RXXR, resulting in the generation and secretion of biologically active molecules (Bragdon et al., 2011; Cui et al., 1998; Goldman et al., 2006; Shimasaki et al., 2004). As with other TGFbeta family members, BMP4 is a cysteine knot-containing, disulfide-linked dimer (Jones et al., 1994; Shimasaki et al., 2004), containing a conserved TGF-beta propeptide domain (pfam00668) and transforming growth factor beta like domain (cl02510). One high-throughput study has identified a ubiquitination site at Lys-185 (Kim et al., 2011).
Expression The amino acid sequence for BMP4 was first derived from an isolated preparation of bovine bone (Wozney et al., 1988). Human BMP4 was cloned from a placental cDNA library (Oida et al., 1995). Apart from its high expression in developing embryonic tissues (Chen et al., 2004), BMP4 was determined by microarray analysis to be highly expressed in adult tissues such as the thymus, spleen, brain, heart, muscle, kidney, lung, liver, pancreas, and prostate (Schmueli et al., 2003; Yanai et al., 2005). Immunohistochemical analysis of adult tissues shows high expression in epithelial cells of the skin, bladder and stomach (Alarmo et al., 2012). In tumors, BMP4 is expressed in melanoma, ovarian, gastric, basal cell, renal and squamous carcinomas of the head and neck (Chiu et al., 2012; Deng et al., 2007; Davies et al., 2008; Giacomini et al., 2006; Johnson et al., 2009; Kim et al., 2011; Kwak et al., 2007; Laatio et al., 2011; Lombardo et al., 2011; Sneddon et al., 2006; Rothhammer et al., 2005; Xu et al., 2011). Overexpression of BMP4 in comparison to normal tissues is observed in breast, ovarian, gastric, hepatocellular and colorectal carcinomas (Alarmo et al., 2012; Chiu et al., 2012; Deng et al., 2007; Kim et al., 2011).
Localisation BMP4 is a secreted protein localized within the extracellular milieu (Chen et al., 2004), but has also been shown to localize within the cytoplasm in vesicles directed for lysosomal degradation, in order to tightly mitigate BMP4 signalling (Kelley et al., 2009).
Function BMP4 is a member of the bone morphogenetic protein family, which is part of the transforming growth factor-beta superfamily of growth and differentiation factors. Bone morphogenetic proteins were originally identified by an ability of demineralized bone extract to induce endochondral osteogenesis in vivo in an extraskeletal site (Urist, 1965), but are now considered essential factors with varying roles during embryogenesis, skeletal formation, hematopoiesis and neurogenesis (Bragdon et al., 2001; Chen et al., 2004; Kallioniemi, 2012). In adult tissues, BMP4 signalling can control many cellular behaviours including differentiation, proliferation, apoptosis, and motility (Kallioniemi, 2012).
The mature BMP4 dimer binds to type I and II serine-threonine kinase receptors, and the constitutively active BMP type II receptor will phosphorylate the type I receptor upon ligand binding (Miyazono et al., 2010; Nohe et al., 2004). The activated type I BMP receptor is then able to phosphorylate the cytosolic receptor-regulated SMAD proteins (Attisano et al., 2000; Bragdon et al., 2001; Miyazono et al., 2010), which will then form a complex with the common SMAD4, translocate to the nucleus to regulate gene transcription (Feng et al., 2005; ten Dijke et al., 2003). In addition to this canonical SMAD-dependent signaling pathway, BMP4 can signal through SMAD-independent means to directly induce ERK and p38 MAPKs, JNK, NFkB, PI3K, PKA, PKC and PKD signaling pathways affecting cell survival, apoptosis, migration and differentiation (Bragdon et al., 2011). In addition to intracellular regulation, BMP4 signals can be modulated at the receptor level through interaction with three different type I (BMPR1A [ALK3], BMPR1B [ALK6], and ACVR1A [ALK2]) and type II (BMPR2, ACVR2A [Act-RII], and ACVR2B [Act-RIIB]) receptors (Kawabata et al., 1998; Miyazono et al., 2010; Nohe et al., 2004), and negatively regulated by interaction with the pseudoreceptor BAMBI (Onichtchouk et al., 1999). BMP4 signalling can also be regulated at the extracellular level through binding to the endogenous inhibitors tsg (Twisted gastrulation) and Follistatin, and those belonging to the Dan family (Dan, Gremlin, Gremlin2, Cerberus, Coco, Caronte, Ectodin, and Sclerostin), and the Chordin family (Chordin, Chordin-like-2, Noggin) of BMP antagonists (Bragdon et al., 2011).
Homology There are BMP4 homologs in several vertebrate species, including chimpanzee, rhesus monkey, dog, cow, chicken, rat, mouse, lizard, frog (Xenopus laevis), and zebrafish (Danio rerio) and in invertebrates such as the fruit fly (Drosophila melanogaster) and the worm (Caenorhabditis elegans).

Mutations

Germinal Heterozygous mutations in exons 3 and 4 of the BMP4 gene resulting in decreased expression were found in children with cleft lip and cleft palate (Suzuki et al., 2009), including: a 1037C-T transition resulting in an A346V substitution; a 271A-T transversion resulting in a S91C substitution; a 860G-A transition resulting in an R287H substitution; and a 592C-T transition resulting in an R198X substitution.
Three pathogenic germline mutations were identified in a cohort of 504 genetically enriched colorectal cancer cases. p.R286X (g.8330C>T) localizes to the N-terminal of the prodomain truncating the protein prior to the active domain; p.W325C (g.8449G>T) and p.C373S (g.8592G>C) mutations are predicted from protein homology modelling with BMP2 to impact deleteriously on BMP4 function; and p.C373S (g.8592G>C) segregates with adenoma and hyperplastic polyps in first-degree relatives, suggesting this germline mutation may confer a juvenile polyposis-type phenotype (Lubbe et al., 2011).
Somatic Four substitution missense mutations have been identified: two mutations were detected in two different single prostate tumors (c.344A>T, p.N115I (Grasso et al., 2012), c.857G>A, p.R286Q (Barbieri et al., 2012), and two in two different large intestinal carcinoma tumors (c.631C>T, p.R211W, and c.1222C>T, p.R408C)) (The Cancer Genome Atlas Network, 2012).

Implicated in

Entity Fibrodysplasia ossificans progressiva (FOP)
Prognosis Fibrodysplasia ossificans progressiva (FOP) is an extremely rare and disabling autosomal dominant genetic disorder with complete penetrance characterized by congenital malformations of the great toes and by progressive heterotopic endochondral ossification in predictable anatomical patterns. Ectopic expression of BMP-4 was found in FOP patients (Gannon et al., 1997; Xu et al., 2000).
Cytogenetics Overexpression of BMP4 mRNA was found in FOP patients (Shafritz et al., 1996), in addition a heterozygous activating mutation found in the ACVR1 gene (Shore et al., 2006).
  
Entity Microphthalmia, syndromic 6 (MCOPS6)
Prognosis A loss of BMP4 expression can lead to the heritable disorder microphthalmia syndromic type 6 (MCOPS6); also known as microphthalmia and pituitary anomalies or microphthalmia with brain and digit developmental anomalies. Microphthalmia is a clinically heterogeneous disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). MCOPS6 is characterized by microphthalmia/anophthalmia associated with facial, genital, skeletal, neurologic and endocrine anomalies. (Bakrania et al., 2008; Bennett et al., 1991; Elliott et al., 1993; Lemyre et al., 1998; Phadke et al., 1994).
Cytogenetics Deletions in 14q22-q23 are associated with anophthalmia-microphthalmia, brain, pituitary, and ear anomalies including structural defects and hearing loss, hypothyroidism, poly- and/or syndactyly, clinodactyly, high arched palate, cryptorchidism, and developmental delay (Ahmad et al., 2003; Bennett et al., 1991).
  
Entity Oral Facial Cleft 11 (OFC11)
Prognosis Mutations in the BMP4 gene during development can result in congenital 'healed' cleft lip (CHCL), an unusual heritable anomaly consisting of a paramedian 'scar' of the upper lip with an appearance suggesting that a typical cleft lip was corrected in utero. The CHCL is frequently associated with an ipsilateral notch in the vermilion border and a 'collapsed' nostril (Castilla et al., 1995).
Cytogenetics Missense and nonsense mutations in the BMP4 gene resulting in decreased expression were found in children with cleft lip and cleft palate (Suzuki et al., 2009).
  
Entity Basal-cell carcinoma
Oncogenesis BMP4 treatment of primary cultures of basal carcinoma cells reduces cell growth and induces the expression of keratinocyte differentiation markers, which can be antagonized by the BMP inhibitor gremlin1 (Sneddon et al., 2006).
  
Entity Bladder cancer
Oncogenesis BMP4 inhibits growth in the RT4 cell line, but no effect is seen in TCC-Sup or TSU-Pr1 cells; expression of BMPR2 in TSU-Pr1 cells restores the growth-inhibitory effect of BMP4 treatment in nude mice (Kim et al., 2004). Through the mining of publicly available whole genome microarray datasets, BMP4 was identified within a set of 17 differentially expressed genes to be downregulated in bladder cancers (Zaravinos et al., 2011).
  
Entity Brain cancers
Oncogenesis BMP4 increased growth and reduced apoptosis of the neuroectodermal tumor cell line DAOY (Iantosca et al., 1999). Treatment of glioblastoma stem cells with BMP4 decreased proliferation and induced differentiation in GBM cells (Piccirillo et al., 2006), cerebellar granule neuron progenitors (GNPs) and primary GNP-like medulloblastoma cells (Zhao et al., 2008), and inhibited glioma stem cell proliferation via G1 arrest and CCND1 while enhancing apoptosis through induction of Bax and inhibition of Bcl-2 and Bcl-xL (Zhou et al., 2011). BMP4-dependent growth inhibitory effects were also seen in the brain glioma cell line U251 (Liu et al., 2011). BMP4 is expressed in meningiomas, and stimulates the proliferative capacity of primary meningioma cell cultures via phosphorylation of Smad 1, but not p38 MAPK (Johnson et al., 2009). Human astrocytomas were found to have methylation of the BMP4 promoter (Wu et al., 2010).
  
Entity Breast cancer
Prognosis BMP4 is highly expressed in primary breast cancer tumors and cell lines (Alarmo et al., 2007), and strong immunohistochemical expression of BMP4 correlates significantly with reduced proliferation and increased rates of recurrence (Alarmo et al., 2012). Methylation of the BMP4 promoter, combined within a four-gene methylation signature, was found predictive of outcome in steroid receptor-positive, node-negative, HER-2 negative breast cancer patients treated with anthracycline (Hartmann et al., 2009).
Oncogenesis Exogenous treatment of BMP4 abrogates lumen formation in mammary epithelial cells and promotes invasive growth (Montesano, 2007). BMP4 treatment did not affect the proliferative capacity of immortalized mammary epithelial cells, however BMP4 potentiates growth factor-induced proliferation (Montesano et al., 2008). BMP4 treatment of MDA-MB-231 and MCF-7 breast carcinoma cells inhibited MMP expression and activity, decreasing their metastatic potential (Shon et al., 2009). In nine breast cancer cell lines, BMP4 treatment induced growth suppression via G1 arrest, while stimulating cell migration and invasion in a SMAD-dependent manner (Ketolainen et al., 2010). BMP4 treatment of MDA-MB-231 and MCF-7 breast cancer cell lines induced migration and invasion phenotypes via the upregulation of MMP-1 and CXCR4 that could be abrogated by either anti-BMP4 siRNA or Noggin treatment (Guo et al., 2012). BMP4 treatment of multiple breast cancer cell lines and analysis using a whole genome oligo microarray revealed a strong transcriptional response for genes involved in cellular differentiation and transcriptional activity (Rodriguez-Martinez et al., 2011).
  
Entity Colorectal carcinoma (CRC)
Prognosis Three germline pathogenic mutations of BMP4, p.R286X (g.8330C>T), p.W325C (g.8449G>T) and p.C373S (g.8592G>C) were suggested to be causal for colorectal cancer (Lubbe et al., 2011). Three common variants (rs4444235, rs17563, and rs1957636) at the BMP4 locus have been associated with elevated risk of colorectal cancer (Houlston et al., 2008; Lubbe et al., 2012; Slattery et al., 2012; Theodoratou et al., 2012; Tomlinson et al., 2011). Immunohistochemical and real-time mRNA expression analysis of BMP4 in primary tumors correlated strongly with advanced stage and liver metastases (Deng et al., 2007).
Oncogenesis Germline BMP4 mutations were found to be deleterious to the BMP4 protein in colorectal cancers (Lubbe et al., 2011). Furthermore, a common polymorphism found within the distal BMP4 promoter (17 kb upstream) acts as a cis-acting enhancer of BMP4 transcription, leading to enhanced expression, which is significantly associated with colorectal cancer risk (Lubbe et al., 2012). Overexpression of BMP4 in HCT116 human colorectal cancer cell line promotes in vitro migration and invasion (Deng et al., 2007). In colorectal stem cells isolated from primary tumors, BMP4 treatment induced terminal differentiation, apoptosis and chemosensitization in vitro and in tumour xenografts (Lombardo et al., 2011). BMP4 signalling has been shown to protect HCT116 cells from heat-induced apoptosis by modulating MAPK pathways (Deng et al., 2007), and overexpression of BMP4 can enhance the invasiveness of CRC cells independent of Smad4 activity (Deng et al., 2009).
  
Entity Gastric cancer (GC)
Prognosis Expression of BMP4 is inversely related to prevalence of lymph node metastasis in gastric adenocarcinomas (Kim et al., 2011). BMP4 mRNA was significantly overexpressed in gastric cancers relative to mucosal controls and negatively correlated with BMP4 promoter methylation, while high expression of BMP4 predicted poor outcome (Ivanova et al., 2012).
Oncogenesis Immunocytochemical analysis of primary gastric tumors revealed that BMP4 was significantly overexpressed in comparison to normal mucosa, and correlated with Helicobater pylori infection. However, the expression of BMP4 negatively correlated with the presence of lymph node metastases and tumor invasiveness (Kim et al., 2011). BMP4 is highly expressed in cisplatin-resistant cell lines, and overexpression induced GC cell line tumorigenicity in vitro, while shRNA-mediated knockdown decreased proliferation, colony formation and restored cisplatin sensitivity (Ivanova et al., 2012). In diffuse-type gastric carcinoma cells lines in vitro, BMP4 acted as a tumor suppressor by inducing cell cycle arrest in these cells via p21 induction through the SMAD pathway (Shirai et al., 2011).
  
Entity Hepatocellular carcinoma (HCC)
Prognosis BMP4 is significantly overexpressed in 60% of primary HCC tumors (Chiu et al., 2012). BMP4 immunohistochemical expression significantly correlated with increased tumor nodules, increasing TMN stage, vascular invasion and tumor invasiveness, and was an independent predictor of disease-free and overall survival in HCC patients (Guo et al., 2012).
Oncogenesis BMP4 promotes the growth and migration of HCC cell lines in vitro, and BMP4 can induce cyclin-dependent kinase 1 (CDK1) and cyclin B1 upregulation to accelerate cell-cycle progression and metastasis in HCC cells through MEK-ERK signaling (Chiu et al., 2012). In HCC cell lines, BMP4 expression was shown to be induced by hypoxia to promote in vitro migration, invasion, anchorage-independence and tube formation to promote tumor progression (Maegdefrau et al., 2009).
  
Entity Lung cancer
Prognosis Combined with 3 other biomarkers, immunohistochemical expression of BMP4 was shown to predict the risk of bone metastasis in stage III resected non-small cell lung carcinoma (Zhou et al., 2012).
Oncogenesis Treatment of lung cancer cell line A549 with BMP4 induced a senescent phenotype, characterized by reduced growth, increased size, reduced invasion, and expression of senescence-associated beta-galactosidase. BMP4-treated A549 cells also exhibited decreased growth in mouse xenograft models (Buckley et al., 2004). BMP4 via Smad signalling has also been shown to mediate adriamycin-induced premature senescence in multiple lung carcinoma cell lines (Su et al., 2009). A later study found that cooperativity between p38 MAPK and Smad pathways is required for BMP4-induced senescence (Su et al., 2011).
  
Entity Melanoma
Prognosis Bioinformatics analyses identified polymorphisms within the BMP4 gene (SNPs 6007 C/T (rs17563) and 3445 T/G (rs4898820)) affecting mRNA expression and shows a significant association with cutaneous melanoma (Capasso et al., 2009).
Oncogenesis BMP4 was found to be overexpressed in melanoma cell lines, and primary and metastatic melanomas compared to nevi. Although no effect was seen on proliferation, BMP4 signalling significanctly increased migration and invasion in melanoma cell lines (Rothhammer et al., 2005). BMP4 was later shown to stimulate angiogenesis in malignant melanomas by inducing tube formation as well as the migratory efficiency of microvascular endothelial cells (Rothhammer et al., 2007).
  
Entity Multiple myeloma
Oncogenesis BMP4 inhibited DNA synthesis and induced G1 arrest and/or apoptosis in OH-2, IH-1 and ANBL-6 cell lines (Hjertner et al., 2001), and induced apoptosis in multiple myeloma cell lines via Smad-dependent down-regulation of MYC (Holien et al., 2012). However, BMP4 was shown to be overexpressed in bone marrow cells derived from multiple myeloma patients, and partially protected myeloma cells from apoptosis induced by the anti-myeloma drug bortezomib (a proteosome inhibitor) (Grcevic et al., 2010).
  
Entity Ovarian cancer
Prognosis One study identified via immunohistochemistry that high BMP4 expression in primary serous ovarian cancer tumors was an independent prognostic factor for longer progression-free survival time and overall survival prior to administration of chemotherapy (Laatio et al., 2011).
Oncogenesis An autocrine BMP signalling pathway was identified in primary human ovarian surface epithelial cells and primary ovarian cancer cells. Treatment of primary ovarian cancer cells with BMP4 had no effect on proliferative capacity, but long-term cultures showed decreased cell density and increased cell spreading and adherence (Shepherd et al., 2003). Treatment of primary ovarian cancer cells with exogenous BMP4 produced morphological alterations and increased cellular adhesion, motility and invasion, which could be inhibited by Noggin, while primary ovarian surface epithelial cells showed no response to these ligands (Thériault et al., 2007). BMP4 treatment also altered the EMT markers Snail, Slug and E-cadherin, along with an increase in activation of Rho-GTPases, suggesting that ovarian cancer agressive cellular behaviours may be mediated through autocrine BMP4 signalling (Thériault et al., 2007). These BMP4-induced changes in cellular morphology and motility were later found to be Smad-dependent (é et al., 2011). Ovarian cancer tumor-associated mesenchymal stem cells were found to have overexpression of BMP4, suggesting BMP4 may have a role in modulation of the tumor microenvironment to promote tumorigenesis (McLean et al., 2011).
  
Entity Pancreatic cancer
Cytogenetics A CGH study of pancreatic primary tumors, cell lines and xenografts determined a significant recurrent low-level gain of chromosome 14q22.2 in these samples (Nowak, et al., 2005).
Oncogenesis BMP4 demonstrates overexpression at the mRNA level in 25% of 16 established pancreatic cell lines compared to normal tissues. Treatment of 5 cell lines with BMP4 induced growth suppression via G1 arrest, but significantly increased the migratory and invasive phenotypes of pancreatic cell lines (3 out of 5) in vitro via SMAD-dependent signalling (Virtanen et al., 2011). BMP4 treatment of Panc-1 cells induced an EMT response characterized by increased migration mediated by MSX2 induction (Hamada et al., 2007), while another study demonstrated BMP4 treatment of Panc-1 cells also resulted in an EMT response involving MMP2 activity that was Smad1-dependent (Gordon et al., 2009).
  
Entity Prostate cancer
Prognosis Immunohistochemical analysis of primary prostate cancer tumors and bone metastases revealed that BMP4 was overexpressed in the metastatic deposits, but not the primary tumors suggesting a role for BMP4 expression in promoting prostate cancer metastasis (Spanjol et al., 2010).
Oncogenesis Treatment of LNCaP cells with BMP4 inhibited proliferation through G1 arrest and induction of p21, however no effect on growth was seen in PC-3 cells (Brubaker et al., 2004). Another study confirmed the growth inhibitory effect of BMP4 on LNCaP cells and found the effect could be abrogated by Noggin treatment (Shaw et al., 2010). In LAPC-4 cells, BMP4 treatment showed no effect on cellular proliferation, migration or invasion (Feeley et al., 2005). However a later study found that BMP4 could promote prostate tumor growth in bone through osteogenesis in the xenograft cell line MDA-PCa-118b (Lee et al., 2011).
  
Entity Pituitary tumors
Oncogenesis BMP4 has cell-type specific effects on pituitary cells (Labeur et al., 2010). BMP4 signalling was determined to stimulate proliferation and MYC expression in pituitary prolactinomas but not in other pituitary tumors, along with promoting tumorigenic growth of rat GH3 cells in nude mice (Paez-Pereda et al., 2003). BMP4 expression is reduced in corticotrophinomas from Cushing's patients in comparison to normal corticotroph cells, while BMP4 treatment of mouse AtT-20 corticotroph cells showed no effect on proliferation, but transfection of the BMP4 inhibitor Noggin stimulated tumorigenic growth in nude mice (Giacomini et al., 2006).
  
Entity Renal cell carcinoma (RCC)
Prognosis Immunohistochemical analysis of RCC tumors demonstrated BMP4 overexpression in 44%, however no prognostic value could be associated with BMP4 expression (Kwak et al., 2007). BMP4 mRNA expression was significantly higher in non-clear cell RCCs than clear cell RCCs, however no association of BMP4 expression with survival was found (Markic et al., 2011).
Oncogenesis The BMP4 promoter was hypermethylated, resulting in downregulated expression in 35% of primary RCC tumors tested (Ricketts et al., 2012).
  
Entity Retinoblastoma
Oncogenesis BMP4 signalling was intact, and exogenous treatment increased caspase-independent apoptosis in the RB1-deficient cell line WERI-Rb1, while no effect on proliferation was seen (Haubold et al., 2010).
  
Entity Various cancers
Note Numerous microarray studies indexed in Oncomine (oncomine.org) document altered expression of BMP4 in other cancers, including head and neck cancers, cervical cancers and lymphomas and sarcomas.
  

External links

Nomenclature
HGNC (Hugo)BMP4   1071
Cards
AtlasBMP4ID811ch14q22
Entrez_Gene (NCBI)BMP4  652  bone morphogenetic protein 4
GeneCards (Weizmann)BMP4
Ensembl (Hinxton)ENSG00000125378 [Gene_View]  chr14:54416455-54423554 [Contig_View]  BMP4 [Vega]
ICGC DataPortalENSG00000125378
cBioPortalBMP4
AceView (NCBI)BMP4
Genatlas (Paris)BMP4
WikiGenes652
SOURCE (Princeton)NM_001202 NM_130850 NM_130851
Genomic and cartography
GoldenPath (UCSC)BMP4  -  14q22.2   chr14:54416455-54423554 -  14q22-q23   [Description]    (hg19-Feb_2009)
EnsemblBMP4 - 14q22-q23 [CytoView]
Mapping of homologs : NCBIBMP4 [Mapview]
OMIM112262   600625   607932   
Gene and transcription
Genbank (Entrez)BC020546 BQ083000 BU683974 BX161385 BX161438
RefSeq transcript (Entrez)NM_001202 NM_130850 NM_130851
RefSeq genomic (Entrez)AC_000146 NC_000014 NC_018925 NG_009215 NT_026437 NW_001838111 NW_004929393
Consensus coding sequences : CCDS (NCBI)BMP4
Cluster EST : UnigeneHs.68879 [ NCBI ]
CGAP (NCI)Hs.68879
Alternative Splicing : Fast-db (Paris)GSHG0009375
Alternative Splicing GalleryENSG00000125378
Gene ExpressionBMP4 [ NCBI-GEO ]     BMP4 [ SEEK ]   BMP4 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP12644 (Uniprot)
NextProtP12644  [Medical]
With graphics : InterProP12644
Splice isoforms : SwissVarP12644 (Swissvar)
Domaine pattern : Prosite (Expaxy)TGF_BETA_1 (PS00250)    TGF_BETA_2 (PS51362)   
Domains : Interpro (EBI)TGF-b_C [organisation]   TGF-b_N [organisation]   TGF-beta-rel [organisation]   TGFb_CS [organisation]  
Related proteins : CluSTrP12644
Domain families : Pfam (Sanger)TGF_beta (PF00019)    TGFb_propeptide (PF00688)   
Domain families : Pfam (NCBI)pfam00019    pfam00688   
Domain families : Smart (EMBL)TGFB (SM00204)  
DMDM Disease mutations652
Blocks (Seattle)P12644
Human Protein AtlasENSG00000125378 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP12644
HPRD00207
IPIIPI00292640   
Protein Interaction databases
DIP (DOE-UCLA)P12644
IntAct (EBI)P12644
FunCoupENSG00000125378
BioGRIDBMP4
InParanoidP12644
Interologous Interaction database P12644
IntegromeDBBMP4
STRING (EMBL)BMP4
Ontologies - Pathways
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  activation of MAPKK activity  osteoblast differentiation  ureteric bud development  branching involved in ureteric bud morphogenesis  kidney development  mesonephros development  neural tube closure  positive regulation of protein phosphorylation  positive regulation of endothelial cell proliferation  endochondral ossification  blood vessel endothelial cell proliferation involved in sprouting angiogenesis  chondrocyte differentiation  hematopoietic progenitor cell differentiation  lymphoid progenitor cell differentiation  renal system process  BMP signaling pathway involved in heart induction  secondary heart field specification  endocardial cushion development  cardiac septum development  type B pancreatic cell development  mesenchymal to epithelial transition involved in metanephros morphogenesis  cytokine activity  protein binding  extracellular region  extracellular region  proteinaceous extracellular matrix  extracellular space  common-partner SMAD protein phosphorylation  smoothened signaling pathway  germ cell development  mesodermal cell fate determination  growth factor activity  heparin binding  negative regulation of cell proliferation  post-embryonic development  anterior/posterior axis specification  specification of organ position  positive regulation of endothelial cell migration  positive regulation of pathway-restricted SMAD protein phosphorylation  positive regulation of pathway-restricted SMAD protein phosphorylation  positive regulation of cell death  telencephalon development  dorsal/ventral neural tube patterning  telencephalon regionalization  pituitary gland development  extracellular matrix organization  erythrocyte differentiation  monocyte differentiation  macrophage differentiation  positive regulation of bone mineralization  BMP signaling pathway  BMP signaling pathway  positive regulation of BMP signaling pathway  negative regulation of chondrocyte differentiation  positive regulation of collagen biosynthetic process  negative regulation of T cell differentiation in thymus  negative regulation of immature T cell proliferation in thymus  protein localization to nucleus  embryonic hindlimb morphogenesis  tendon cell differentiation  deltoid tuberosity development  chemoattractant activity  negative regulation of phosphorylation  odontogenesis of dentin-containing tooth  odontogenesis  regulation of odontogenesis of dentin-containing tooth  embryonic digit morphogenesis  positive regulation of apoptotic process  negative regulation of apoptotic process  steroid hormone mediated signaling pathway  negative regulation of MAP kinase activity  positive regulation of endothelial cell differentiation  negative regulation of myoblast differentiation  positive regulation of neuron differentiation  positive regulation of osteoblast differentiation  positive regulation of ossification  negative regulation of cell cycle  negative regulation of mitosis  negative regulation of striated muscle tissue development  negative regulation of transcription, DNA-dependent  positive regulation of transcription, DNA-dependent  positive regulation of transcription from RNA polymerase II promoter  lung alveolus development  intermediate mesodermal cell differentiation  positive regulation of smooth muscle cell proliferation  neuron fate commitment  embryonic cranial skeleton morphogenesis  smooth muscle tissue development  branching morphogenesis of an epithelial tube  positive regulation of epithelial cell proliferation  negative regulation of epithelial cell proliferation  positive chemotaxis  regulation of smooth muscle cell differentiation  cardiac muscle cell differentiation  positive regulation of cardiac muscle fiber development  inner ear receptor cell differentiation  cloacal septation  lens induction in camera-type eye  embryonic skeletal joint morphogenesis  cranial suture morphogenesis  positive regulation of SMAD protein import into nucleus  regulation of pathway-restricted SMAD protein phosphorylation  SMAD protein signal transduction  lung morphogenesis  bronchus development  trachea development  trachea formation  epithelial tube branching involved in lung morphogenesis  branching involved in prostate gland morphogenesis  bud elongation involved in lung branching  epithelial cell proliferation involved in lung morphogenesis  bud dilation involved in lung branching  negative regulation of cell death  mammary gland formation  epithelial-mesenchymal cell signaling  negative regulation of prostatic bud formation  regulation of branching involved in prostate gland morphogenesis  positive regulation of cartilage development  positive regulation of branching involved in lung morphogenesis  BMP signaling pathway involved in ureter morphogenesis  BMP signaling pathway involved in renal system segmentation  pulmonary artery endothelial tube morphogenesis  negative regulation of thymocyte apoptotic process  positive regulation of ERK1 and ERK2 cascade  BMP receptor binding  cellular response to growth factor stimulus  BMP signaling pathway involved in nephric duct formation  renal system development  glomerular visceral epithelial cell development  negative regulation of branch elongation involved in ureteric bud branching by BMP signaling pathway  specification of ureteric bud anterior/posterior symmetry by BMP signaling pathway  glomerular capillary formation  negative regulation of glomerular mesangial cell proliferation  mesenchymal cell proliferation involved in ureteric bud development  mesenchymal cell differentiation involved in kidney development  ureter epithelial cell differentiation  ureter smooth muscle cell differentiation  mesenchymal cell proliferation involved in ureter development  negative regulation of mesenchymal cell proliferation involved in ureter development  metanephric collecting duct development  positive regulation of kidney development  negative regulation of branching involved in ureteric bud morphogenesis  negative regulation of glomerulus development  negative regulation of metanephric S-shaped body morphogenesis  negative regulation of metanephric comma-shaped body morphogenesis  positive regulation of DNA-dependent DNA replication  negative regulation of cell proliferation involved in heart morphogenesis  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  activation of MAPKK activity  osteoblast differentiation  ureteric bud development  branching involved in ureteric bud morphogenesis  kidney development  mesonephros development  neural tube closure  positive regulation of protein phosphorylation  positive regulation of endothelial cell proliferation  endochondral ossification  blood vessel endothelial cell proliferation involved in sprouting angiogenesis  chondrocyte differentiation  hematopoietic progenitor cell differentiation  lymphoid progenitor cell differentiation  renal system process  BMP signaling pathway involved in heart induction  secondary heart field specification  endocardial cushion development  cardiac septum development  type B pancreatic cell development  mesenchymal to epithelial transition involved in metanephros morphogenesis  cytokine activity  protein binding  extracellular region  extracellular region  proteinaceous extracellular matrix  extracellular space  common-partner SMAD protein phosphorylation  smoothened signaling pathway  germ cell development  mesodermal cell fate determination  growth factor activity  heparin binding  negative regulation of cell proliferation  post-embryonic development  anterior/posterior axis specification  specification of organ position  positive regulation of endothelial cell migration  positive regulation of pathway-restricted SMAD protein phosphorylation  positive regulation of pathway-restricted SMAD protein phosphorylation  positive regulation of cell death  telencephalon development  dorsal/ventral neural tube patterning  telencephalon regionalization  pituitary gland development  extracellular matrix organization  erythrocyte differentiation  monocyte differentiation  macrophage differentiation  positive regulation of bone mineralization  BMP signaling pathway  BMP signaling pathway  positive regulation of BMP signaling pathway  negative regulation of chondrocyte differentiation  positive regulation of collagen biosynthetic process  negative regulation of T cell differentiation in thymus  negative regulation of immature T cell proliferation in thymus  protein localization to nucleus  embryonic hindlimb morphogenesis  tendon cell differentiation  deltoid tuberosity development  chemoattractant activity  negative regulation of phosphorylation  odontogenesis of dentin-containing tooth  odontogenesis  regulation of odontogenesis of dentin-containing tooth  embryonic digit morphogenesis  positive regulation of apoptotic process  negative regulation of apoptotic process  steroid hormone mediated signaling pathway  negative regulation of MAP kinase activity  positive regulation of endothelial cell differentiation  negative regulation of myoblast differentiation  positive regulation of neuron differentiation  positive regulation of osteoblast differentiation  positive regulation of ossification  negative regulation of cell cycle  negative regulation of mitosis  negative regulation of striated muscle tissue development  negative regulation of transcription, DNA-dependent  positive regulation of transcription, DNA-dependent  positive regulation of transcription from RNA polymerase II promoter  lung alveolus development  intermediate mesodermal cell differentiation  positive regulation of smooth muscle cell proliferation  neuron fate commitment  embryonic cranial skeleton morphogenesis  smooth muscle tissue development  branching morphogenesis of an epithelial tube  positive regulation of epithelial cell proliferation  negative regulation of epithelial cell proliferation  positive chemotaxis  regulation of smooth muscle cell differentiation  cardiac muscle cell differentiation  positive regulation of cardiac muscle fiber development  inner ear receptor cell differentiation  cloacal septation  lens induction in camera-type eye  embryonic skeletal joint morphogenesis  cranial suture morphogenesis  positive regulation of SMAD protein import into nucleus  regulation of pathway-restricted SMAD protein phosphorylation  SMAD protein signal transduction  lung morphogenesis  bronchus development  trachea development  trachea formation  epithelial tube branching involved in lung morphogenesis  branching involved in prostate gland morphogenesis  bud elongation involved in lung branching  epithelial cell proliferation involved in lung morphogenesis  bud dilation involved in lung branching  negative regulation of cell death  mammary gland formation  epithelial-mesenchymal cell signaling  negative regulation of prostatic bud formation  regulation of branching involved in prostate gland morphogenesis  positive regulation of cartilage development  positive regulation of branching involved in lung morphogenesis  BMP signaling pathway involved in ureter morphogenesis  BMP signaling pathway involved in renal system segmentation  pulmonary artery endothelial tube morphogenesis  negative regulation of thymocyte apoptotic process  positive regulation of ERK1 and ERK2 cascade  BMP receptor binding  cellular response to growth factor stimulus  BMP signaling pathway involved in nephric duct formation  renal system development  glomerular visceral epithelial cell development  negative regulation of branch elongation involved in ureteric bud branching by BMP signaling pathway  specification of ureteric bud anterior/posterior symmetry by BMP signaling pathway  glomerular capillary formation  negative regulation of glomerular mesangial cell proliferation  mesenchymal cell proliferation involved in ureteric bud development  mesenchymal cell differentiation involved in kidney development  ureter epithelial cell differentiation  ureter smooth muscle cell differentiation  mesenchymal cell proliferation involved in ureter development  negative regulation of mesenchymal cell proliferation involved in ureter development  metanephric collecting duct development  positive regulation of kidney development  negative regulation of branching involved in ureteric bud morphogenesis  negative regulation of glomerulus development  negative regulation of metanephric S-shaped body morphogenesis  negative regulation of metanephric comma-shaped body morphogenesis  positive regulation of DNA-dependent DNA replication  negative regulation of cell proliferation involved in heart morphogenesis  
Pathways : BIOCARTAALK in cardiac myocytes [Genes]   
Pathways : KEGGHedgehog signaling pathway    TGF-beta signaling pathway    Hippo signaling pathway    Thyroid hormone signaling pathway    Pathways in cancer    Basal cell carcinoma   
Protein Interaction DatabaseBMP4
Wikipedia pathwaysBMP4
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)BMP4
snp3D : Map Gene to Disease652
SNP (GeneSNP Utah)BMP4
SNP : HGBaseBMP4
Genetic variants : HAPMAPBMP4
Exome VariantBMP4
1000_GenomesBMP4 
ICGC programENSG00000125378 
Somatic Mutations in Cancer : COSMICBMP4 
CONAN: Copy Number AnalysisBMP4 
Mutations and Diseases : HGMDBMP4
Genomic VariantsBMP4  BMP4 [DGVbeta]
dbVarBMP4
ClinVarBMP4
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM112262    600625    607932   
MedgenBMP4
GENETestsBMP4
Disease Genetic AssociationBMP4
Huge Navigator BMP4 [HugePedia]  BMP4 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneBMP4
Homology/Alignments : Family Browser (UCSC)BMP4
Phylogenetic Trees/Animal Genes : TreeFamBMP4
Chemical/Protein Interactions : CTD652
Chemical/Pharm GKB GenePA25381
Clinical trialBMP4
Cancer Resource (Charite)ENSG00000125378
Other databases
Other databasePhosphoSitePlus
Probes
Litterature
PubMed271 Pubmed reference(s) in Entrez
CoreMineBMP4
iHOPBMP4

Bibliography

Bone: formation by autoinduction.
Urist MR.
Science. 1965 Nov 12;150(3698):893-9.
PMID 5319761
 
Novel regulators of bone formation: molecular clones and activities.
Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM, Wang EA.
Science. 1988 Dec 16;242(4885):1528-34.
PMID 3201241
 
Deletion 14q (q22q23) associated with anophthalmia, absent pituitary, and other abnormalities.
Bennett CP, Betts DR, Seller MJ.
J Med Genet. 1991 Apr;28(4):280-1.
PMID 1856837
 
DVR-4 (bone morphogenetic protein-4) as a posterior-ventralizing factor in Xenopus mesoderm induction.
Jones CM, Lyons KM, Lapan PM, Wright CV, Hogan BL.
Development. 1992 Jun;115(2):639-47.
PMID 1425343
 
A case of deletion 14(q22.1-->q22.3) associated with anophthalmia and pituitary abnormalities.
Elliott J, Maltby EL, Reynolds B.
J Med Genet. 1993 Mar;30(3):251-2. (REVIEW)
PMID 7682620
 
Murine bone morphogenetic protein-4 gene: existence of multiple promoters and exons for the 5'-untranslated region.
Kurihara T, Kitamura K, Takaoka K, Nakazato H.
Biochem Biophys Res Commun. 1993 May 14;192(3):1049-56.
PMID 8507180
 
Osteogenic protein-1 (OP-1) expression and processing in Chinese hamster ovary cells: isolation of a soluble complex containing the mature and pro-domains of OP-1.
Jones WK, Richmond EA, White K, Sasak H, Kusmik W, Smart J, Oppermann H, Rueger DC, Tucker RF.
Growth Factors. 1994;11(3):215-25.
PMID 7734147
 
Anophthalmia with cleft palate and micrognathia: a new syndrome?
Phadke SR, Sharma AK, Agarwal SS.
J Med Genet. 1994 Dec;31(12):960-1.
PMID 7891380
 
Congenital healed cleft lip.
Castilla EE, Martinez-Frias ML.
Am J Med Genet. 1995 Aug 28;58(2):106-12.
PMID 8533798
 
The mouse bone morphogenetic protein-4 gene. Analysis of promoter utilization in fetal rat calvarial osteoblasts and regulation by COUP-TFI orphan receptor.
Feng JQ, Chen D, Cooney AJ, Tsai MJ, Harris MA, Tsai SY, Feng M, Mundy GR, Harris SE.
J Biol Chem. 1995 Nov 24;270(47):28364-73.
PMID 7499338
 
Cloning and sequence of bone morphogenetic protein 4 (BMP-4) from a human placental cDNA library.
Oida S, Iimura T, Maruoka Y, Takeda K, Sasaki S.
DNA Seq. 1995;5(5):273-5.
PMID 7579580
 
The Xvent-2 homeobox gene is part of the BMP-4 signalling pathway controlling [correction of controling] dorsoventral patterning of Xenopus mesoderm.
Onichtchouk D, Gawantka V, Dosch R, Delius H, Hirschfeld K, Blumenstock C, Niehrs C.
Development. 1996 Oct;122(10):3045-53.
PMID 8898218
 
Regulation of dorsal-ventral patterning: the ventralizing effects of the novel Xenopus homeobox gene Vox.
Schmidt JE, von Dassow G, Kimelman D.
Development. 1996 Jun;122(6):1711-21.
PMID 8674411
 
Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva.
Shafritz AB, Shore EM, Gannon FH, Zasloff MA, Taub R, Muenke M, Kaplan FS.
N Engl J Med. 1996 Aug 22;335(8):555-61.
PMID 8678932
 
Genomic organization of the human bone morphogenetic protein-4 gene: molecular basis for multiple transcripts.
van den Wijngaard A, van Kraay M, van Zoelen EJ, Olijve W, Boersma CJ.
Biochem Biophys Res Commun. 1996 Feb 27;219(3):789-94.
PMID 8645259
 
Transcriptional regulation of the mBMP-4 gene through an E-box in the 5'-flanking promoter region involving USF.
Ebara S, Kawasaki S, Nakamura I, Tsutsumimoto T, Nakayama K, Nikaido T, Takaoka K.
Biochem Biophys Res Commun. 1997 Nov 7;240(1):136-41.
PMID 9367898
 
Bone morphogenetic protein 2/4 in early fibromatous lesions of fibrodysplasia ossificans progressiva.
Gannon FH, Kaplan FS, Olmsted E, Finkel GC, Zasloff MA, Shore E.
Hum Pathol. 1997 Mar;28(3):339-43.
PMID 9042799
 
BMP-4 is proteolytically activated by furin and/or PC6 during vertebrate embryonic development.
Cui Y, Jean F, Thomas G, Christian JL.
EMBO J. 1998 Aug 17;17(16):4735-43.
PMID 9707432
 
Signal transduction by bone morphogenetic proteins.
Kawabata M, Imamura T, Miyazono K.
Cytokine Growth Factor Rev. 1998 Mar;9(1):49-61. (REVIEW)
PMID 9720756
 
Transcriptional regulation of BMP-4 in the Xenopus embryo: analysis of genomic BMP-4 and its promoter.
Kim J, Ault KT, Chen HD, Xu RH, Roh DH, Lin MC, Park MJ, Kung HF.
Biochem Biophys Res Commun. 1998 Sep 18;250(2):516-30.
PMID 9753664
 
Del(14)(q22.1q23.2) in a patient with anophthalmia and pituitary hypoplasia.
Lemyre E, Lemieux N, Decarie JC, Lambert M.
Am J Med Genet. 1998 May 1;77(2):162-5. (REVIEW)
PMID 9605291
 
The human bone morphogenetic protein 4 (BMP-4) gene: molecular structure and transcriptional regulation.
Shore EM, Xu M, Shah PB, Janoff HB, Hahn GV, Deardorff MA, Sovinsky L, Spinner NB, Zasloff MA, Wozney JM, Kaplan FS.
Calcif Tissue Int. 1998 Sep;63(3):221-9.
PMID 9701626
 
Bone morphogenetic proteins-2 and -4 attenuate apoptosis in a cerebellar primitive neuroectodermal tumor cell line.
Iantosca MR, McPherson CE, Ho SY, Maxwell GD.
J Neurosci Res. 1999 May 1;56(3):248-58.
PMID 10336254
 
Silencing of TGF-beta signalling by the pseudoreceptor BAMBI.
Onichtchouk D, Chen YG, Dosch R, Gawantka V, Delius H, Massague J, Niehrs C.
Nature. 1999 Sep 30;401(6752):480-5.
PMID 10519551
 
Smads as transcriptional co-modulators.
Attisano L, Wrana JL.
Curr Opin Cell Biol. 2000 Apr;12(2):235-43. (REVIEW)
PMID 10712925
 
Regulation of the promoters for the human bone morphogenetic protein 2 and 4 genes.
Helvering LM, Sharp RL, Ou X, Geiser AG.
Gene. 2000 Oct 3;256(1-2):123-38.
PMID 11054542
 
Linkage exclusion and mutational analysis of the noggin gene in patients with fibrodysplasia ossificans progressiva (FOP).
Xu MQ, Feldman G, Le Merrer M, Shugart YY, Glaser DL, Urtizberea JA, Fardeau M, Connor JM, Triffitt J, Smith R, Shore EM, Kaplan FS.
Clin Genet. 2000 Oct;58(4):291-8.
PMID 11076054
 
Bone morphogenetic protein-4 inhibits proliferation and induces apoptosis of multiple myeloma cells.
Hjertner O, Hjorth-Hansen H, Borset M, Seidel C, Waage A, Sundan A.
Blood. 2001 Jan 15;97(2):516-22.
PMID 11154231
 
14q(22) deletion in a familial case of anophthalmia with polydactyly.
Ahmad ME, Dada R, Dada T, Kucheria K.
Am J Med Genet A. 2003 Jul 1;120A(1):117-22.
PMID 12794703
 
Transcriptional activation of BMP-4 and regulation of mammalian organogenesis by GATA-4 and -6.
Nemer G, Nemer M.
Dev Biol. 2003 Feb 1;254(1):131-48.
PMID 12606287
 
Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk.
Paez-Pereda M, Giacomini D, Refojo D, Nagashima AC, Hopfner U, Grubler Y, Chervin A, Goldberg V, Goya R, Hentges ST, Low MJ, Holsboer F, Stalla GK, Arzt E.
Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1034-9. Epub 2003 Jan 27.
PMID 12552124
 
Identification of a putative autocrine bone morphogenetic protein-signaling pathway in human ovarian surface epithelium and ovarian cancer cells.
Shepherd TG, Nachtigal MW.
Endocrinology. 2003 Aug;144(8):3306-14.
PMID 12865307
 
GeneNote: whole genome expression profiles in normal human tissues.
Shmueli O, Horn-Saban S, Chalifa-Caspi V, Shmoish M, Ophir R, Benjamin-Rodrig H, Safran M, Domany E, Lancet D.
C R Biol. 2003 Oct-Nov;326(10-11):1067-72.
PMID 14744114
 
Controlling cell fate by bone morphogenetic protein receptors.
ten Dijke P, Korchynskyi O, Valdimarsdottir G, Goumans MJ.
Mol Cell Endocrinol. 2003 Dec 15;211(1-2):105-13. (REVIEW)
PMID 14656483
 
Bone morphogenetic protein signaling in prostate cancer cell lines.
Brubaker KD, Corey E, Brown LG, Vessella RL.
J Cell Biochem. 2004 Jan 1;91(1):151-60.
PMID 14689587
 
BMP4 signaling induces senescence and modulates the oncogenic phenotype of A549 lung adenocarcinoma cells.
Buckley S, Shi W, Driscoll B, Ferrario A, Anderson K, Warburton D.
Am J Physiol Lung Cell Mol Physiol. 2004 Jan;286(1):L81-6. Epub 2003 Sep 5.
PMID 12959928
 
Bone morphogenetic proteins.
Chen D, Zhao M, Mundy GR.
Growth Factors. 2004 Dec;22(4):233-41. (REVIEW)
PMID 15621726
 
Restoration of bone morphogenetic protein receptor type II expression leads to a decreased rate of tumor growth in bladder transitional cell carcinoma cell line TSU-Pr1.
Kim IY, Lee DH, Lee DK, Kim WJ, Kim MM, Morton RA, Lerner SP, Kim SJ.
Cancer Res. 2004 Oct 15;64(20):7355-60.
PMID 15492256
 
Signal transduction of bone morphogenetic protein receptors.
Nohe A, Keating E, Knaus P, Petersen NO.
Cell Signal. 2004 Mar;16(3):291-9. (REVIEW)
PMID 14687659
 
The bone morphogenetic protein system in mammalian reproduction.
Shimasaki S, Moore RK, Otsuka F, Erickson GF.
Endocr Rev. 2004 Feb;25(1):72-101. (REVIEW)
PMID 14769828
 
Influence of BMPs on the formation of osteoblastic lesions in metastatic prostate cancer.
Feeley BT, Gamradt SC, Hsu WK, Liu N, Krenek L, Robbins P, Huard J, Lieberman JR.
J Bone Miner Res. 2005 Dec;20(12):2189-99. Epub 2005 Aug 1.
PMID 16294272
 
Specificity and versatility in tgf-beta signaling through Smads.
Feng XH, Derynck R.
Annu Rev Cell Dev Biol. 2005;21:659-93. (REVIEW)
PMID 16212511
 
Genome-wide aberrations in pancreatic adenocarcinoma.
Nowak NJ, Gaile D, Conroy JM, McQuaid D, Cowell J, Carter R, Goggins MG, Hruban RH, Maitra A.
Cancer Genet Cytogenet. 2005 Aug;161(1):36-50.
PMID 16080956
 
Bone morphogenic proteins are overexpressed in malignant melanoma and promote cell invasion and migration.
Rothhammer T, Poser I, Soncin F, Bataille F, Moser M, Bosserhoff AK.
Cancer Res. 2005 Jan 15;65(2):448-56.
PMID 15695386
 
Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification.
Yanai I, Benjamin H, Shmoish M, Chalifa-Caspi V, Shklar M, Ophir R, Bar-Even A, Horn-Saban S, Safran M, Domany E, Lancet D, Shmueli O.
Bioinformatics. 2005 Mar 1;21(5):650-9. Epub 2004 Sep 23.
PMID 15388519
 
Bone morphogenetic protein-4 inhibits corticotroph tumor cells: involvement in the retinoic acid inhibitory action.
Giacomini D, Paez-Pereda M, Theodoropoulou M, Labeur M, Refojo D, Gerez J, Chervin A, Berner S, Losa M, Buchfelder M, Renner U, Stalla GK, Arzt E.
Endocrinology. 2006 Jan;147(1):247-56. Epub 2005 Sep 29.
PMID 16195406
 
Mutation of an upstream cleavage site in the BMP4 prodomain leads to tissue-specific loss of activity.
Goldman DC, Hackenmiller R, Nakayama T, Sopory S, Wong C, Kulessa H, Christian JL.
Development. 2006 May;133(10):1933-42. Epub 2006 Apr 19.
PMID 16624858
 
Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells.
Piccirillo SG, Reynolds BA, Zanetti N, Lamorte G, Binda E, Broggi G, Brem H, Olivi A, Dimeco F, Vescovi AL.
Nature. 2006 Dec 7;444(7120):761-5.
PMID 17151667
 
A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva.
Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ, Choi IH, Connor JM, Delai P, Glaser DL, LeMerrer M, Morhart R, Rogers JG, Smith R, Triffitt JT, Urtizberea JA, Zasloff M, Brown MA, Kaplan FS.
Nat Genet. 2006 May;38(5):525-7. Epub 2006 Apr 23.
PMID 16642017
 
Bone morphogenetic protein antagonist gremlin 1 is widely expressed by cancer-associated stromal cells and can promote tumor cell proliferation.
Sneddon JB, Zhen HH, Montgomery K, van de Rijn M, Tward AD, West R, Gladstone H, Chang HY, Morganroth GS, Oro AE, Brown PO.
Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14842-7. Epub 2006 Sep 26.
PMID 17003113
 
A comprehensive expression survey of bone morphogenetic proteins in breast cancer highlights the importance of BMP4 and BMP7.
Alarmo EL, Kuukasjarvi T, Karhu R, Kallioniemi A.
Breast Cancer Res Treat. 2007 Jun;103(2):239-46. Epub 2006 Sep 21.
PMID 17004110
 
Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells.
Deng H, Makizumi R, Ravikumar TS, Dong H, Yang W, Yang WL.
Exp Cell Res. 2007 Mar 10;313(5):1033-44. Epub 2007 Jan 10.
PMID 17275810
 
Bone morphogenetic protein-4 inhibits heat-induced apoptosis by modulating MAPK pathways in human colon cancer HCT116 cells.
Deng H, Ravikumar TS, Yang WL.
Cancer Lett. 2007 Oct 28;256(2):207-17. Epub 2007 Jul 20.
PMID 17640799
 
Bone morphogenetic protein 4 induces epithelial-mesenchymal transition through MSX2 induction on pancreatic cancer cell line.
Hamada S, Satoh K, Hirota M, Kimura K, Kanno A, Masamune A, Shimosegawa T.
J Cell Physiol. 2007 Dec;213(3):768-74.
PMID 17516553
 
Expression of bone morphogenetic proteins, the subfamily of the transforming growth factor-beta superfamily, in renal cell carcinoma.
Kwak C, Park YH, Kim IY, Moon KC, Ku JH.
J Urol. 2007 Sep;178(3 Pt 1):1062-7. Epub 2007 Jul 20.
PMID 17644140
 
Bone morphogenetic protein-4 abrogates lumen formation by mammary epithelial cells and promotes invasive growth.
Montesano R.
Biochem Biophys Res Commun. 2007 Feb 16;353(3):817-22. Epub 2006 Dec 22.
PMID 17189614
 
Functional implication of BMP4 expression on angiogenesis in malignant melanoma.
Rothhammer T, Bataille F, Spruss T, Eissner G, Bosserhoff AK.
Oncogene. 2007 Jun 14;26(28):4158-70. Epub 2006 Dec 18.
PMID 17173062
 
BMP4 induces EMT and Rho GTPase activation in human ovarian cancer cells.
Theriault BL, Shepherd TG, Mujoomdar ML, Nachtigal MW.
Carcinogenesis. 2007 Jun;28(6):1153-62. Epub 2007 Feb 1.
PMID 17272306
 
Mutations in BMP4 cause eye, brain, and digit developmental anomalies: overlap between the BMP4 and hedgehog signaling pathways.
Bakrania P, Efthymiou M, Klein JC, Salt A, Bunyan DJ, Wyatt A, Ponting CP, Martin A, Williams S, Lindley V, Gilmore J, Restori M, Robson AG, Neveu MM, Holder GE, Collin JR, Robinson DO, Farndon P, Johansen-Berg H, Gerrelli D, Ragge NK.
Am J Hum Genet. 2008 Feb;82(2):304-19. doi: 10.1016/j.ajhg.2007.09.023. Epub 2008 Jan 31.
PMID 18252212
 
Bone morphogenetic proteins 1 to 7 in human breast cancer, expression pattern and clinical/prognostic relevance.
Davies SR, Watkins G, Douglas-Jones A, Mansel RE, Jiang WG.
J Exp Ther Oncol. 2008;7(4):327-38.
PMID 19227012
 
Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer.
Houlston RS, Webb E, Broderick P, Pittman AM, Di Bernardo MC, Lubbe S, Chandler I, Vijayakrishnan J, Sullivan K, Penegar S; Colorectal Cancer Association Study Consortium, Carvajal-Carmona L, Howarth K, Jaeger E, Spain SL, Walther A, Barclay E, Martin L, Gorman M, Domingo E, Teixeira AS; CoRGI Consortium, Kerr D, Cazier JB, Niittymaki I, Tuupanen S, Karhu A, Aaltonen LA, Tomlinson IP, Farrington SM, Tenesa A, Prendergast JG, Barnetson RA, Cetnarskyj R, Porteous ME, Pharoah PD, Koessler T, Hampe J, Buch S, Schafmayer C, Tepel J, Schreiber S, Volzke H, Chang-Claude J, Hoffmeister M, Brenner H, Zanke BW, Montpetit A, Hudson TJ, Gallinger S; International Colorectal Cancer Genetic Association Consortium, Campbell H, Dunlop MG.
Nat Genet. 2008 Dec;40(12):1426-35. doi: 10.1038/ng.262. Epub 2008 Nov 16.
PMID 19011631
 
Bone morphogenetic protein-4 strongly potentiates growth factor-induced proliferation of mammary epithelial cells.
Montesano R, Sarkozi R, Schramek H.
Biochem Biophys Res Commun. 2008 Sep 12;374(1):164-8. doi: 10.1016/j.bbrc.2008.07.007. Epub 2008 Jul 14.
PMID 18625198
 
Role of the transcriptional corepressor Bcor in embryonic stem cell differentiation and early embryonic development.
Wamstad JA, Corcoran CM, Keating AM, Bardwell VJ.
PLoS One. 2008 Jul 30;3(7):e2814. doi: 10.1371/journal.pone.0002814.
PMID 18795143
 
Post-transcriptional down-regulation of Atoh1/Math1 by bone morphogenic proteins suppresses medulloblastoma development.
Zhao H, Ayrault O, Zindy F, Kim JH, Roussel MF.
Genes Dev. 2008 Mar 15;22(6):722-7. doi: 10.1101/gad.1636408.
PMID 18347090
 
A predicted functional single-nucleotide polymorphism of bone morphogenetic protein-4 gene affects mRNA expression and shows a significant association with cutaneous melanoma in Southern Italian population.
Capasso M, Ayala F, Russo R, Avvisati RA, Asci R, Iolascon A.
J Cancer Res Clin Oncol. 2009 Dec;135(12):1799-807. doi: 10.1007/s00432-009-0628-y. Epub 2009 Jun 26.
PMID 19557432
 
Identification of an ancient Bmp4 mesoderm enhancer located 46 kb from the promoter.
Chandler KJ, Chandler RL, Mortlock DP.
Dev Biol. 2009 Mar 15;327(2):590-602. doi: 10.1016/j.ydbio.2008.12.033. Epub 2009 Jan 3.
PMID 19159624
 
Overexpression of bone morphogenetic protein 4 enhances the invasiveness of Smad4-deficient human colorectal cancer cells.
Deng H, Ravikumar TS, Yang WL.
Cancer Lett. 2009 Aug 28;281(2):220-31. doi: 10.1016/j.canlet.2009.02.046. Epub 2009 Mar 24.
PMID 19321257
 
Bone morphogenetic proteins induce pancreatic cancer cell invasiveness through a Smad1-dependent mechanism that involves matrix metalloproteinase-2.
Gordon KJ, Kirkbride KC, How T, Blobe GC.
Carcinogenesis. 2009 Feb;30(2):238-48. doi: 10.1093/carcin/bgn274. Epub 2008 Dec 4.
PMID 19056927
 
DNA methylation markers predict outcome in node-positive, estrogen receptor-positive breast cancer with adjuvant anthracycline-based chemotherapy.
Hartmann O, Spyratos F, Harbeck N, Dietrich D, Fassbender A, Schmitt M, Eppenberger-Castori S, Vuaroqueaux V, Lerebours F, Welzel K, Maier S, Plum A, Niemann S, Foekens JA, Lesche R, Martens JW.
Clin Cancer Res. 2009 Jan 1;15(1):315-23. doi: 10.1158/1078-0432.CCR-08-0166.
PMID 19118060
 
Bone morphogenetic protein 4 and its receptors are expressed in the leptomeninges and meningiomas and signal via the Smad pathway.
Johnson MD, O'Connell MJ, Vito F, Pilcher W.
J Neuropathol Exp Neurol. 2009 Nov;68(11):1177-83. doi: 10.1097/NEN.0b013e3181bc6642.
PMID 19816200
 
A concentration-dependent endocytic trap and sink mechanism converts Bmper from an activator to an inhibitor of Bmp signaling.
Kelley R, Ren R, Pi X, Wu Y, Moreno I, Willis M, Moser M, Ross M, Podkowa M, Attisano L, Patterson C.
J Cell Biol. 2009 Feb 23;184(4):597-609. doi: 10.1083/jcb.200808064. Epub 2009 Feb 16.
PMID 19221194
 
Bone morphogenetic protein 4 is induced in hepatocellular carcinoma by hypoxia and promotes tumour progression.
Maegdefrau U, Amann T, Winklmeier A, Braig S, Schubert T, Weiss TS, Schardt K, Warnecke C, Hellerbrand C, Bosserhoff AK.
J Pathol. 2009 Aug;218(4):520-9. doi: 10.1002/path.2563.
PMID 19431154
 
Control of BMP gene expression by long-range regulatory elements.
Pregizer S, Mortlock DP.
Cytokine Growth Factor Rev. 2009 Oct-Dec;20(5-6):509-15. doi: 10.1016/j.cytogfr.2009.10.011. Epub 2009 Nov 8. (REVIEW)
PMID 19900834
 
Bone morphogenetic protein-4 induced by NDRG2 expression inhibits MMP-9 activity in breast cancer cells.
Shon SK, Kim A, Kim JY, Kim KI, Yang Y, Lim JS.
Biochem Biophys Res Commun. 2009 Jul 24;385(2):198-203. doi: 10.1016/j.bbrc.2009.05.038. Epub 2009 May 19.
PMID 19450561
 
BMP4-Smad signaling pathway mediates adriamycin-induced premature senescence in lung cancer cells.
Su D, Zhu S, Han X, Feng Y, Huang H, Ren G, Pan L, Zhang Y, Lu J, Huang B.
J Biol Chem. 2009 May 1;284(18):12153-64. doi: 10.1074/jbc.M807930200. Epub 2009 Mar 6.
PMID 19269967
 
Mutations in BMP4 are associated with subepithelial, microform, and overt cleft lip.
Suzuki S, Marazita ML, Cooper ME, Miwa N, Hing A, Jugessur A, Natsume N, Shimozato K, Ohbayashi N, Suzuki Y, Niimi T, Minami K, Yamamoto M, Altannamar TJ, Erkhembaatar T, Furukawa H, Daack-Hirsch S, L'heureux J, Brandon CA, Weinberg SM, Neiswanger K, Deleyiannis FW, de Salamanca JE, Vieira AR, Lidral AC, Martin JF, Murray JC.
Am J Hum Genet. 2009 Mar;84(3):406-11. doi: 10.1016/j.ajhg.2009.02.002. Epub 2009 Feb 26.
PMID 19249007
 
Bone morphogenetic proteins and receptors are over-expressed in bone-marrow cells of multiple myeloma patients and support myeloma cells by inducing ID genes.
Grcevic D, Kusec R, Kovacic N, Lukic A, Lukic IK, Ivcevic S, Nemet D, Seiwerth RS, Ostojic SK, Croucher PI, Marusic A.
Leuk Res. 2010 Jun;34(6):742-51. doi: 10.1016/j.leukres.2009.10.016. Epub 2009 Nov 18.
PMID 19926132
 
Bone morphogenetic protein 4 (BMP4) signaling in retinoblastoma cells.
Haubold M, Weise A, Stephan H, Dunker N.
Int J Biol Sci. 2010 Nov 24;6(7):700-15.
PMID 21152263
 
Parallel inhibition of cell growth and induction of cell migration and invasion in breast cancer cells by bone morphogenetic protein 4.
Ketolainen JM, Alarmo EL, Tuominen VJ, Kallioniemi A.
Breast Cancer Res Treat. 2010 Nov;124(2):377-86. doi: 10.1007/s10549-010-0808-0. Epub 2010 Feb 25.
PMID 20182795
 
Pituitary tumors: cell type-specific roles for BMP-4.
Labeur M, Paez-Pereda M, Haedo M, Arzt E, Stalla GK.
Mol Cell Endocrinol. 2010 Sep 15;326(1-2):85-8. doi: 10.1016/j.mce.2010.04.006. Epub 2010 Apr 14. (REVIEW)
PMID 20398728
 
Effect of bone morphogenetic protein 4 in the human brain glioma cell line U251.
Liu B, Tian D, Yi W, Wu L, Cai Q, Dong H, Shen H, Ji B, Wang L, Zhang S, Ruan D, Chen Q.
Cell Biochem Biophys. 2010 Nov;58(2):91-6. doi: 10.1007/s12013-010-9095-y.
PMID 20730570
 
Bone morphogenetic protein receptors and signal transduction.
Miyazono K, Kamiya Y, Morikawa M.
J Biochem. 2010 Jan;147(1):35-51. doi: 10.1093/jb/mvp148. Epub 2009 Sep 17. (REVIEW)
PMID 19762341
 
An FGF4-FRS2alpha-Cdx2 axis in trophoblast stem cells induces Bmp4 to regulate proper growth of early mouse embryos.
Murohashi M, Nakamura T, Tanaka S, Ichise T, Yoshida N, Yamamoto T, Shibuya M, Schlessinger J, Gotoh N.
Stem Cells. 2010 Jan;28(1):113-21. doi: 10.1002/stem.247.
PMID 19890878
 
Shox2 mediates Tbx5 activity by regulating Bmp4 in the pacemaker region of the developing heart.
Puskaric S, Schmitteckert S, Mori AD, Glaser A, Schneider KU, Bruneau BG, Blaschke RJ, Steinbeisser H, Rappold G.
Hum Mol Genet. 2010 Dec 1;19(23):4625-33. doi: 10.1093/hmg/ddq393. Epub 2010 Sep 21.
PMID 20858598
 
Exploration of Shh and BMP paracrine signaling in a prostate cancer xenograft.
Shaw A, Gipp J, Bushman W.
Differentiation. 2010 Jan;79(1):41-7. doi: 10.1016/j.diff.2009.08.009. Epub 2009 Sep 20.
PMID 19773112
 
Role of bone morphogenetic proteins in human prostate cancer pathogenesis and development of bone metastases: immunohistochemical study.
Spanjol J, Djordjevic G, Markic D, Klaric M, Fuckar D, Bobinac D.
Coll Antropol. 2010 Apr;34 Suppl 2:119-25.
PMID 21302710
 
Hypoxia regulates BMP4 expression in the murine spleen during the recovery from acute anemia.
Wu DC, Paulson RF.
PLoS One. 2010 Jun 24;5(6):e11303. doi: 10.1371/journal.pone.0011303.
PMID 20585586
 
CpG island hypermethylation in human astrocytomas.
Wu X, Rauch TA, Zhong X, Bennett WP, Latif F, Krex D, Pfeifer GP.
Cancer Res. 2010 Apr 1;70(7):2718-27. doi: 10.1158/0008-5472.CAN-09-3631. Epub 2010 Mar 16.
PMID 20233874
 
Bone morphogenetic proteins: a critical review.
Bragdon B, Moseychuk O, Saldanha S, King D, Julian J, Nohe A.
Cell Signal. 2011 Apr;23(4):609-20. doi: 10.1016/j.cellsig.2010.10.003. Epub 2010 Oct 16. (REVIEW)
PMID 20959140
 
Oncogenic KRAS regulates BMP4 expression in colon cancer cell lines.
Duerr EM, Mizukami Y, Moriichi K, Gala M, Jo WS, Kikuchi H, Xavier RJ, Chung DC.
Am J Physiol Gastrointest Liver Physiol. 2012 May 15;302(10):G1223-30. doi: 10.1152/ajpgi.00047.2011. Epub 2012 Mar 1.
PMID 22383492
 
Expression of bone morphogenic protein-4 is inversely related to prevalence of lymph node metastasis in gastric adenocarcinoma.
Kim SG, Park HR, Min SK, Choi JY, Koh SH, Kim JW, Lee HW.
Surg Today. 2011 May;41(5):688-92. doi: 10.1007/s00595-010-4320-2. Epub 2011 May 1.
PMID 21533942
 
Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. doi: 10.1016/j.molcel.2011.08.025. Epub 2011 Sep 8.
PMID 21906983
 
BMP-4 expression has prognostic significance in advanced serous ovarian carcinoma and is affected by cisplatin in OVCAR-3 cells.
Laatio L, Myllynen P, Serpi R, Rysa J, Ilves M, Lappi-Blanco E, Ruskoaho H, Vahakangas K, Puistola U.
Tumour Biol. 2011 Oct;32(5):985-95. doi: 10.1007/s13277-011-0200-7. Epub 2011 Jun 15.
PMID 21674241
 
BMP4 promotes prostate tumor growth in bone through osteogenesis.
Lee YC, Cheng CJ, Bilen MA, Lu JF, Satcher RL, Yu-Lee LY, Gallick GE, Maity SN, Lin SH.
Cancer Res. 2011 Aug 1;71(15):5194-203. doi: 10.1158/0008-5472.CAN-10-4374. Epub 2011 Jun 13.
PMID 21670081
 
Bone morphogenetic protein 4 induces differentiation of colorectal cancer stem cells and increases their response to chemotherapy in mice.
Lombardo Y, Scopelliti A, Cammareri P, Todaro M, Iovino F, Ricci-Vitiani L, Gulotta G, Dieli F, de Maria R, Stassi G.
Gastroenterology. 2011 Jan;140(1):297-309. doi: 10.1053/j.gastro.2010.10.005. Epub 2010 Oct 14.
PMID 20951698
 
Evaluation of germline BMP4 mutation as a cause of colorectal cancer.
Lubbe SJ, Pittman AM, Matijssen C, Twiss P, Olver B, Lloyd A, Qureshi M, Brown N, Nye E, Stamp G, Blagg J, Houlston RS.
Hum Mutat. 2011 Jan;32(1):E1928-38. doi: 10.1002/humu.21376. Epub 2010 Oct 14.
PMID 20949628
 
mRNA expression of bone morphogenetic proteins and their receptors in human renal cell carcinoma.
Markic D, Celic T, Grskovic A, Spanjol J, Fuckar Z, Grahovac B, Dordevic G, Bobinac D.
Urol Int. 2011;87(3):353-8. doi: 10.1159/000330797. Epub 2011 Aug 26.
PMID 21876344
 
Human ovarian carcinoma-associated mesenchymal stem cells regulate cancer stem cells and tumorigenesis via altered BMP production.
McLean K, Gong Y, Choi Y, Deng N, Yang K, Bai S, Cabrera L, Keller E, McCauley L, Cho KR, Buckanovich RJ.
J Clin Invest. 2011 Aug;121(8):3206-19. doi: 10.1172/JCI45273.
PMID 21737876
 
Analysis of BMP4 and BMP7 signaling in breast cancer cells unveils time-dependent transcription patterns and highlights a common synexpression group of genes.
Rodriguez-Martinez A, Alarmo EL, Saarinen L, Ketolainen J, Nousiainen K, Hautaniemi S, Kallioniemi A.
BMC Med Genomics. 2011 Nov 25;4:80. doi: 10.1186/1755-8794-4-80.
PMID 22118688
 
Bone morphogenetic protein-2 and -4 play tumor suppressive roles in human diffuse-type gastric carcinoma.
Shirai YT, Ehata S, Yashiro M, Yanagihara K, Hirakawa K, Miyazono K.
Am J Pathol. 2011 Dec;179(6):2920-30. doi: 10.1016/j.ajpath.2011.08.022. Epub 2011 Oct 11.
PMID 21996676
 
Role of p38 MAPK pathway in BMP4-mediated Smad-dependent premature senescence in lung cancer cells.
Su D, Peng X, Zhu S, Huang Y, Dong Z, Zhang Y, Zhang J, Liang Q, Lu J, Huang B.
Biochem J. 2011 Jan 15;433(2):333-43. doi: 10.1042/BJ20100404.
PMID 21050181
 
Human ovarian cancer cell morphology, motility, and proliferation are differentially influenced by autocrine TGFβ superfamily signalling.
Theriault BL, Nachtigal MW.
Cancer Lett. 2011 Dec 26;313(1):108-21. doi: 10.1016/j.canlet.2011.08.033. Epub 2011 Sep 10.
PMID 21945631
 
Multiple common susceptibility variants near BMP pathway loci GREM1, BMP4, and BMP2 explain part of the missing heritability of colorectal cancer.
Tomlinson IP, Carvajal-Carmona LG, Dobbins SE, Tenesa A, Jones AM, Howarth K, Palles C, Broderick P, Jaeger EE, Farrington S, Lewis A, Prendergast JG, Pittman AM, Theodoratou E, Olver B, Walker M, Penegar S, Barclay E, Whiffin N, Martin L, Ballereau S, Lloyd A, Gorman M, Lubbe S; COGENT Consortium; CORGI Collaborators; EPICOLON Consortium, Howie B, Marchini J, Ruiz-Ponte C, Fernandez-Rozadilla C, Castells A, Carracedo A, Castellvi-Bel S, Duggan D, Conti D, Cazier JB, Campbell H, Sieber O, Lipton L, Gibbs P, Martin NG, Montgomery GW, Young J, Baird PN, Gallinger S, Newcomb P, Hopper J, Jenkins MA, Aaltonen LA, Kerr DJ, Cheadle J, Pharoah P, Casey G, Houlston RS, Dunlop MG.
PLoS Genet. 2011 Jun;7(6):e1002105. doi: 10.1371/journal.pgen.1002105. Epub 2011 Jun 2.
PMID 21655089
 
Bone morphogenetic protein -4 and -5 in pancreatic cancer--novel bidirectional players.
Virtanen S, Alarmo EL, Sandstrom S, Ampuja M, Kallioniemi A.
Exp Cell Res. 2011 Sep 10;317(15):2136-46. doi: 10.1016/j.yexcr.2011.06.001. Epub 2011 Jun 17.
PMID 21704030
 
Transcriptional regulation of bone morphogenetic protein 4 by tumor necrosis factor and its relationship with age-related macular degeneration.
Xu J, Zhu D, He S, Spee C, Ryan SJ, Hinton DR.
FASEB J. 2011 Jul;25(7):2221-33. doi: 10.1096/fj.10-178350. Epub 2011 Mar 16.
PMID 21411747
 
Bone morphogenetic protein-4-induced epithelial-mesenchymal transition and invasiveness through Smad1-mediated signal pathway in squamous cell carcinoma of the head and neck.
Xu T, Yu CY, Sun JJ, Liu Y, Wang XW, Pi LM, Tian YQ, Zhang X.
Arch Med Res. 2011 Feb;42(2):128-37. doi: 10.1016/j.arcmed.2011.03.003.
PMID 21565626
 
Identification of common differentially expressed genes in urinary bladder cancer.
Zaravinos A, Lambrou GI, Boulalas I, Delakas D, Spandidos DA.
PLoS One. 2011 Apr 4;6(4):e18135. doi: 10.1371/journal.pone.0018135.
PMID 21483740
 
Bone morphogenetic protein 4 inhibits cell proliferation and induces apoptosis in glioma stem cells.
Zhou Z, Sun L, Wang Y, Wu Z, Geng J, Miu W, Pu Y, You Y, Yang Z, Liu N.
Cancer Biother Radiopharm. 2011 Feb;26(1):77-83. doi: 10.1089/cbr.2010.0857.
PMID 21355779
 
Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer.
Barbieri CE, Baca SC, Lawrence MS, Demichelis F, Blattner M, Theurillat JP, White TA, Stojanov P, Van Allen E, Stransky N, Nickerson E, Chae SS, Boysen G, Auclair D, Onofrio RC, Park K, Kitabayashi N, MacDonald TY, Sheikh K, Vuong T, Guiducci C, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Hussain WM, Ramos AH, Winckler W, Redman MC, Ardlie K, Tewari AK, Mosquera JM, Rupp N, Wild PJ, Moch H, Morrissey C, Nelson PS, Kantoff PW, Gabriel SB, Golub TR, Meyerson M, Lander ES, Getz G, Rubin MA, Garraway LA.
Nat Genet. 2012 May 20;44(6):685-9. doi: 10.1038/ng.2279.
PMID 22610119
 
Comprehensive molecular characterization of human colon and rectal cancer.
Cancer Genome Atlas Network.
Nature. 2012 Jul 18;487(7407):330-7. doi: 10.1038/nature11252.
PMID 22810696
 
The activation of MEK/ERK signaling pathway by bone morphogenetic protein 4 to increase hepatocellular carcinoma cell proliferation and migration.
Chiu CY, Kuo KK, Kuo TL, Lee KT, Cheng KH.
Mol Cancer Res. 2012 Mar;10(3):415-27. doi: 10.1158/1541-7786.MCR-11-0293. Epub 2012 Jan 12.
PMID 22241220
 
The mutational landscape of lethal castration-resistant prostate cancer.
Grasso CS, Wu YM, Robinson DR, Cao X, Dhanasekaran SM, Khan AP, Quist MJ, Jing X, Lonigro RJ, Brenner JC, Asangani IA, Ateeq B, Chun SY, Siddiqui J, Sam L, Anstett M, Mehra R, Prensner JR, Palanisamy N, Ryslik GA, Vandin F, Raphael BJ, Kunju LP, Rhodes DR, Pienta KJ, Chinnaiyan AM, Tomlins SA.
Nature. 2012 Jul 12;487(7406):239-43. doi: 10.1038/nature11125.
PMID 22722839
 
Bone morphogenetic protein 4 (BMP4) is required for migration and invasion of breast cancer.
Guo D, Huang J, Gong J.
Mol Cell Biochem. 2012 Apr;363(1-2):179-90. doi: 10.1007/s11010-011-1170-1. Epub 2011 Dec 14.
PMID 22167620
 
Upregulation of bone morphogenetic protein 4 is associated with poor prognosis in patients with hepatocellular carcinoma.
Guo X, Xiong L, Zou L, Zhao J.
Pathol Oncol Res. 2012 Jul;18(3):635-40. doi: 10.1007/s12253-011-9488-2. Epub 2012 Feb 15.
PMID 22350792
 
Bone morphogenetic proteins induce apoptosis in multiple myeloma cells by Smad-dependent repression of MYC.
Holien T, Vatsveen TK, Hella H, Rampa C, Brede G, Groseth LA, Rekvig M, Borset M, Standal T, Waage A, Sundan A.
Leukemia. 2012 May;26(5):1073-80. doi: 10.1038/leu.2011.263. Epub 2011 Sep 23.
PMID 21941367
 
An evolutionarily conserved enhancer regulates Bmp4 expression in developing incisor and limb bud.
Jumlongras D, Lachke SA, O'Connell DJ, Aboukhalil A, Li X, Choe SE, Ho JW, Turbe-Doan A, Robertson EA, Olsen BR, Bulyk ML, Amendt BA, Maas RL.
PLoS One. 2012;7(6):e38568. doi: 10.1371/journal.pone.0038568. Epub 2012 Jun 12.
PMID 22701669
 
Bone morphogenetic protein 4-a fascinating regulator of cancer cell behavior.
Kallioniemi A.
Cancer Genet. 2012 Jun;205(6):267-77. doi: 10.1016/j.cancergen.2012.05.009. (REVIEW)
PMID 22749032
 
The 14q22.2 colorectal cancer variant rs4444235 shows cis-acting regulation of BMP4.
Lubbe SJ, Pittman AM, Olver B, Lloyd A, Vijayakrishnan J, Naranjo S, Dobbins S, Broderick P, Gomez-Skarmeta JL, Houlston RS.
Oncogene. 2012 Aug 16;31(33):3777-84. doi: 10.1038/onc.2011.564. Epub 2011 Dec 12.
PMID 22158048
 
Suppression of Bmp4 signaling by the zinc-finger repressors Osr1 and Osr2 is required for Wnt/β-catenin-mediated lung specification in Xenopus.
Rankin SA, Gallas AL, Neto A, Gomez-Skarmeta JL, Zorn AM.
Development. 2012 Aug;139(16):3010-20. doi: 10.1242/dev.078220. Epub 2012 Jul 12.
PMID 22791896
 
Genome-wide CpG island methylation analysis implicates novel genes in the pathogenesis of renal cell carcinoma.
Ricketts CJ, Morris MR, Gentle D, Brown M, Wake N, Woodward ER, Clarke N, Latif F, Maher ER.
Epigenetics. 2012 Mar;7(3):278-90. doi: 10.4161/epi.7.3.19103.
PMID 22430804
 
Genetic variation in bone morphogenetic protein and colon and rectal cancer.
Slattery ML, Lundgreen A, Herrick JS, Kadlubar S, Caan BJ, Potter JD, Wolff RK.
Int J Cancer. 2012 Feb 1;130(3):653-64. doi: 10.1002/ijc.26047. Epub 2011 Apr 27.
PMID 21387313
 
Systematic meta-analyses and field synopsis of genetic association studies in colorectal cancer.
Theodoratou E, Montazeri Z, Hawken S, Allum GC, Gong J, Tait V, Kirac I, Tazari M, Farrington SM, Demarsh A, Zgaga L, Landry D, Benson HE, Read SH, Rudan I, Tenesa A, Dunlop MG, Campbell H, Little J.
J Natl Cancer Inst. 2012 Oct 3;104(19):1433-57. doi: 10.1093/jnci/djs369. Epub 2012 Sep 26. (REVIEW)
PMID 23019048
 
Establishment of a biomarker model for predicting bone metastasis in resected stage III non-small cell lung cancer.
Zhou Z, Chen ZW, Yang XH, Shen L, Ai XH, Lu S, Luo QQ.
J Exp Clin Cancer Res. 2012 Apr 26;31:34.
PMID 22537906
 
Bone morphogenetic protein 4 expression in multiple normal and tumor tissues reveals its importance beyond development.
Alarmo EL, Huhtala H, Korhonen T, Pylkkanen L, Holli K, Kuukasjarvi T, Parkkila S, Kallioniemi A.
Mod Pathol. 2013 Jan;26(1):10-21. doi: 10.1038/modpathol.2012.128. Epub 2012 Aug 17.
PMID 22899288
 
Integrated epigenomics identifies BMP4 as a modulator of cisplatin sensitivity in gastric cancer.
Ivanova T, Zouridis H, Wu Y, Cheng LL, Tan IB, Gopalakrishnan V, Ooi CH, Lee J, Qin L, Wu J, Lee M, Rha SY, Huang D, Liem N, Yeoh KG, Yong WP, Teh BT, Tan P.
Gut. 2013 Jan;62(1):22-33. doi: 10.1136/gutjnl-2011-301113. Epub 2012 Apr 25.
PMID 22535375
 
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Contributor(s)

Written12-2012Brigitte L Thériault, Mark W Nachtigal
Division of Applied Molecular Oncology, Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada (BLT); Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada (MWN)

Citation

This paper should be referenced as such :
Thériault, BL ; Nachtigal, MW
BMP4 (bone morphogenetic protein 4)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(6):380-390.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/BMP4ID811ch14q22.html

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