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PTHLH (parathyroid hormone-like hormone)

Written2012-07Sai-Ching Jim Yeung, Mouhammed Amir Habra
The University of Texas M. D. Anderson Cancer Center, Department of General Internal Medicine, Ambulatory Treatment, Emergency Care, Department of Endocrine Neoplasia, Hormonal Disorders, 1515 Holcombe Boulevard, Unit 437, Houston, Texas 77030, USA (SCJY); The University of Texas M. D. Anderson Cancer Center, Department of Endocrine Neoplasia, Hormonal Disorders, 1515 Holcombe Boulevard, Unit 1416, Houston, Texas 77030, USA (MAH)
This article is an update of :
2007-10Sai-Ching Jim Yeung
The University of Texas M. D. Anderson Cancer Center, Department of General Internal Medicine, Ambulatory Treatment, Emergency Care, Department of Endocrine Neoplasia, Hormonal Disorders, 1515 Holcombe Boulevard, Unit 437, Houston, Texas 77030, USA

(Note : for Links provided by Atlas : click)


HGNC Alias symbPTHRP
HGNC Alias nameosteostatin
 parathyroid hormone-like hormone preproprotein
 parathyroid hormone-related protein preproprotein
LocusID (NCBI) 5744
Atlas_Id 41897
Location 12p11.22  [Link to chromosome band 12p11]
Location_base_pair Starts at 27958084 and ends at 27969976 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping PTHLH.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
RUNX1 (21q22.12)::PTHLH (12p11.22)


Description PTHLH is encoded by a single gene that is highly conserved among species. The gene is composed of 7 exons spanning a region of 13899 bases (start: 28002284 bp from pter; end: 28016183 bp from pter).
Orientation: minus strand.
The genomic DNA for the PTHLH gene was isolated from a human placental genomic library (Yasuda et al., 1989).
Transcription The sequence is supported by 3 sequences from 3 cDNA clones.
Pseudogene None.


  This diagram represents schematically one possible proteolytic processing pattern of PTHLH into 3 bioactive peptides. The mid-region of PTHLH contains the nuclear localization signal (NLS).
Description Size: 177 amino acids, 20194 Da.
The PTHLH gene has seven exons, and its transcripts are processed by alternative splicing into three isoforms, encoding proteins with 139, 173 and 141 amino acid. The pattern of expression of PTHLH mRNA isoforms may be cell type-specific (Sellers et al., 2004). Although different tumors may have different PTHLH splicing patterns, there are no tumor-specific transcripts (Southby et al., 1995). PTHLH is processed into a set of distinct peptide hormones by endoproteolytic cleavage of the initial translation products: mature N-terminal, mid-region and C-terminal secretory peptides, each having its own distinct function. The distribution of the endopeptidase processing enzymes (PTP (prohormone thiol protease), prohormone convertases 1 and 2 (PC1 and PC2)) may vary in different tissues (Deftos et al., 2001). PTP cleaved the PTHLH precursor at the multibasic, dibasic, and monobasic residue cleavage sites to generate the NH2-terminal peptide (residues 1-37, having PTH-like and growth regulatory activities), the mid-region domain (residues 38-93, regulating calcium transport and cell proliferation), and the COOH-terminal domain (residues 102-141, modulating osteoclast activity) (Hook et al., 2001).
Expression PTHLH is a protein polyhormone produced by most if not all tissues in the body. It is secreted during both fetal and postnatal life. Although PTHLH is found in the circulation, most of its activity appears to be paracrine.
A complex of transcription factors and coactivators (CREB, Ets1 and CBP) regulates PTHLH transcription and may contribute to the alterations associated with the promotion of carcinogenesis (Hamzaoui et al., 2007). Disruption of the normal regulation during cancer progression may in part be associated with TGF-beta1-induced changes in PTHLH mRNA isoform expression and stability (Sellers et al., 2004). TGF-β activates PTHLH expression increasing transcription from the P3 promoter through a synergistic interaction of Smad3 and Ets1 (Lindemann et al., 2001). ERK1/ERK2-dependent Ets2/PKCε synergism also appears to regulate PTHLH expression in breast cancer cells (Lindemann et al., 2003).
The PTHLH gene is also under the transcriptional control of glucocorticoids and vitamin D (Ikeda et al., 1989). 1,25-dihydroxy vitamin D3 treatment increases PTHLH mRNA expression and blocks the stimulatory effect of TGF-beta on PTHLH mRNA expression (Kunakornsawat et al., 2001). Glucocortical steroid hormone can suppress PTHLH mRNA expression and release of bioactive PTHLH in certain PTHLH-producing tumors (Kasono et al., 1991). The regulation of PTHLH expression by female sex steroid hormones is still unclear (Kurebayashi and Soono, 1997; Sugimoto et al., 1999; Rabbani et al., 2005).
Glucocorticoids reduced PTHLH and PTH1R expression in human mesenchymal stem cells which could be one of the mechanisms involved in steroids induced bone loss (Ahlström et al., 2009).
In cell lines, upregulation of hypoxia induced factor HIF-2α subunit is involved in PTHLH upregulation (Manisterski et al., 2010).
PTHLH is a downstream target for RAS and SRC (Li and Drucker, 1994), K-ras mutation increases PTHLH expression (Kamai et al., 2001) while a farnesyltransferase inhibitor known to inhibit RAS function can decrease PTHLH expression (Dackiw et al., 2005). The von Hippel-Lindau tumor suppressor protein also negatively regulates PTHLH expression at the post-transcriptional level (Massfelder et al., 2004).
Localisation PTHLH is a secreted polyhormone and is localized in the Golgi apparatus in the cytoplasm. However, in some cells, PTHLH can be detected in the nucleus by immunochemistry. The growth-inducing effect of NLS-containing mid-region PTHLH peptide in breast cancer is dependent on both internalization into the cytoplasm and subsequent translocation to the nucleus (Kumari et al., 2006). PTHLH travels from the cytosol to the nucleus with the help of the nuclear transport factor importin beta1. Importin beta1 enhanced the association of PTHLH with microtubules, and the microtubule cytoskeleton plays an important role in protein transport to the nucleus (Lam et al., 2002).
The site of recognition of PTHLH is the N-terminal half of importin, which can also bind Ran and nucleoporin, and is sufficient for PTHLH nuclear import (Conti, 2003).
Function PTHLH is a growth factor, a PTH-like calciotropic hormone, a developmental regulatory molecule, and a muscle relaxant (Clemens et al., 2001). The diverse activities of PTHLH result not only from processing of the precursor into multiple hormones, but from use of multiple receptors.
It is clear that the Type 1 Parathyroid Hormone Receptor (PTH1R), binding both PTH (1-34) and PTHLH (1-36), is the receptor mediating the function of PTHLH (1-36), and it is the only cloned receptor for PTHLH so far (Clemens et al., 2001).
PTHLH also binds to a type of receptor in some tissues that does not bind PTH. PTHLH (67-86) activates phospholipase C signaling pathways through a receptor distinct from that activated by PTHLH (1-36) in the same cells (Orloff et al., 1996). Unlike PTH, picomolar concentrations of the PTHLH (107-111) fragment to can activate membrane-associated PKC in osteosarcoma cells (Gagnon et al., 1993). PTHLH (107-139) exerts effects through the PKC/ERK pathway (de Gortázar et al., 2006). Thus, it is highly likely that the mid-region and osteostatin peptides bind other, unique receptors, but those receptors have yet to be cloned and identified.
In contrast to the receptor-mediated endrocrine and paracrine action, the mid-region PTHLH peptide contains a classic bipartite nuclear localization signal (NLS) which upon entering the nuclear compartment confers "intracrine" actions. Details of the nuclear action of PTHLH are still lacking, but overall, nuclear PTHLH appears to be mitogenic (de Miguel et al., 2001). The translation of PTHLH initiates from both the methionine-coding AUG and a leucine-coding CUGs further downstream in its signal sequence. It appeared that when translation was initiated from CUGs, PTHLH accumulated in the nucleoli, and that when translation was initiated from AUG, PTHLH localized in both the Golgi apparatus and nucleoli. Thus, nucleolar PTHLH appears to be derived from translation initiating from both AUG and CUGs (Amizuka et al., 2002). Modulation of cell adhesion by PTHLH localized in the nucleus is a normal physiological action of PTHLH, mediated by increasing integrin gene transcription (Anderson et al., 2007). The promotion by PTHLH in cancer growth and metastasis may be mediated by upregulating integrin alpha6beta4 expression and activating Akt (Shen and Falzon, 2006).
PTHLH also interacts with beta-arrestin 1B, an important component of MAPK signaling and G-protein-coupled receptor desensitization, and this interaction requires residues 122-141 of PTHLH. Therefore, beta-arrestin 1 may mediate a novel regulatory function of PTHLH in intracellular signaling (Conlan et al., 2002).
PTHLH also play a major role in development of several tissues and organs. PTHLH stimulates the proliferation of chondrocytes and suppresses their terminal differentiation. PTHLH (107-139) is a substrate for secPHEX, and osteocalcin, pyrophosphate and phosphate are inhibitors of secPHEX activity; thus PHEX activity and PTHLH are part of a complex network regulating bone mineralization (Boileau et al., 2001). PTHLH plays a central role in the physiological regulation of bone formation, by promoting recruitment and survival of osteoblasts, and probably plays a role in the physiological regulation of bone resorption, by enhancing osteoclast formation. Signaling by fibroblast growth factor receptor 3 and PTHLH coordinate in cartilage and bone development (Amizuka et al., 2004). PTHLH is also an essential physiological regulator of adult bone mass (Bisello et al., 2004).
In oophorectomized mice, injecting PTHLH fragments increased bone formation and reduced bone resorption (de Castro et al., 2012).
Subcutaneous PTHLH injections in healthy postmenopausal women resulted in a pure anabolic effect on bone and increase intestinal calcium absorption when given in high doses (Horwitz et al., 2010).
PTHLH maintains chondrocytes and growth plates as the inhibition of PTHLH signaling via PTH/PTHLH receptor in chondrocytes resulted in an accelerated differentiation of chondrocytes and premature disappearance of the growth plates (Hirai et al., 2011). PTHLH signaling stimulates chrondrocytes proliferation. This process is inhibited via WNT/beta catenin signaling that in turn stimulates chondrocytes hypertrophy (Guo et al., 2009).
In giant cell tumors, stromal cell production of PTHLH increased RANK ligand expression and led to giant cell formation (Cowan et al., 2012).
PTHLH increased the survival of giant cell tumor stromal cells in vitro while the neutralization of PTHLH signaling induced cell death through the activation of different pathways (caspase, TRAIL, JAK-STAT, and cyclin E/CDK2) (Mak et al., 2012).
PTHLH aids in normal mammary gland development and lactation as well as placental transfer of calcium. Mammary gland development depends upon a complex interaction between epithelial and mesenchymal cells that requires PTHLH. The calcium sensor (CaR) regulates PTHLH production as well as transport of calcium in the lactating mammary gland (Ardeshirpour et al., 2006). In normal animals, mammary epithelial cells secrete a lot of PTHLH, which helps to adjust maternal metabolism to meet the calcium demands of lactation. The mid-region PTHLH peptide has also been shown to control the normal maternal-to-fetal pumping of calcium across the placenta.
Rarely, placental PTHLH production can lead to pregnancy associated hypercalcemia. Hypercalcemia in pregnancy could have significant morbidity but tend to resolve post-delivery (Eller-Vainicher et al., 2012).
PTHLH is secreted from smooth muscle in many organs, usually in response to stretching. PTHLH relaxes smooth muscle. Transgenic mice that express PTHLH in vascular smooth muscle have hypotension, being consistent with a vasodilating effect of PTHLH.
PTHLH is highly expressed in the skin. EGF and other similar ligands can potentially activate PTHLH gene expression in the epidermis (Cho et al., 2004). PTHLH can inhibit hair growth and is required for tooth eruption as shown by mouse models that manipulated the PTHLH gene.
In rodent and human pancreatic beta cell cultures, PTHLH (1-36) enhanced the proliferation and function of beta cells. Injecting male mice with PTHLH (1-36) increased beta cell proliferation via increased levels of cyclin D2 and decreased levels of Ink4a (Williams et al., 2011).
PTHLH activates BMP-2/ Cbfa1 signaling pathway which could lead to vascular calcifications in hemodialysis patients (Liu et al., 2012).
In addition, PTHLH overexpression increased arterial vascular smooth muscle cells proliferation resulting in arterial stenosis (Sicari et al., 2012).

Implicated in

Entity Humoral hypercalcemia of malignancy
Prognosis The median survival after the first occurrence of hypercalcemia is 66 days in patients with serum PTHLH ≤ 21 pmol/L and 33 days in patients with PTHLH > 21 pmol/L. In hypercalcemia of malignancy, raised serum levels of PTHLH indicate a more advanced tumor state and an extremely poor prognosis (Pecherstorfer et al., 1994).
Oncogenesis Humoral hypercalcemia of malignancy (HHM) was first described by Albright in 1941 (Albright, 1941), and is a well-known complication among cancer patients. This syndrome is commonly encountered in advanced cancer of epithelial origin, especially squamous cell carcinoma of the lung. Studies of the "humors" secreted by cancer that causes hypercalcemia led to the discovery of 3 classes of peptides: parathyroid-like peptides, growth factor-like peptides, and bone-resorbing factors. Then protein purification led to molecular studies that cloned cDNAs for PTHLH (Suva et al., 1987; Broadus et al., 1988; Mangin et al., 1988). Suva et al. (Suva et al., 1987) suggested that the PTHLH may be responsible for the abnormal calcium metabolism in HHM.
In the mammary epithelium of breast cancer mouse model, PTHLH inhibition delayed tumor formation and spread with reduction of markers of angiogenesis and cell proliferation (Li et al., 2011).
PTHLH can be expressed in many tumors and leads to chemotherapy resistance as it inhibits apoptosis via downregulation of proapoptotic factors including Bax, and PUMA while upregulating antiapoptotic factors (Bcl-2, and Bcl-xl) (Gagiannis et al., 2009).
Entity Autocrine promotion of tumor progression
Prognosis In the absence of hypercalcemia, approximately 17% of patients with gastroesophageal carcinoma have elevated levels of PTHLH, and the increase in PTHLH was associated with a poor prognosis (Deans et al., 2005).
Oncogenesis mRNA for the PTH1R was detected many tumors expressing PTHLH; thus the PTHLH produced by these tumors may act in an autocrine or paracrine fashion (Southby et al., 1995; Alokail and Peddie, 2007; Gessi et al., 2007). PTHLH (1-34) treatment resulted in an increase in proliferation in prostate cancer cells which may require androgen in some cell lines (Asadi et al., 2001). In breast cancer cells, PTHLH regulates CDC2 and CDC25B via PTH1R in a cAMP-independent manner, and PTHLH promotes cell migration through induction of ITGA6, PAI-1, and KISS-1, and promotes proliferation through induction of KISS-1 (Dittmer et al., 2006). These pieces of evidence together suggest that PTHLH and PTH1R together play an important role in the autocrine/paracrine promotion of tumor proliferation in some cancers.
Entity Bone metastasis
Disease Breast cancer
The interactions among breast cancer cells, osteoblasts and osteoclasts define a feedback loop that promote breast cancer growth in the bone microenvironment.
Oncogenesis PTHLH is a mediator of the bone destruction associated with osteolytic metastasis. Patients with PTHLH-expressing breast carcinoma are more likely to develop bone metastasis, and bone metastasis expresses PTHLH in >90% of cases as compared with <20% of cases of metastasis to other sites (Powell et al., 1991).
In breast cancer, osteolytic metastases are the most common. PTHLH is a common osteolytic factor, and other osteolytic factors include vascular endothelial growth factor and interleukin 8 and interleukin 11. Since osteoblasts are the main regulators of osteolytic osteoclasts, stimulation of osteoblasts can paradoxically increase osteoclast function. Simultaneous expression of osteoblastic and osteolytic factors can produce mixed metastases.
PTHLH expression by cancer cells may provide a selective growth advantage in bone because PTHLH stimulates osteoclastic bone resorption to release growth factors such as TGF-beta from the bone matrix. TGF-beta in turn will activate by osteoclastic bone resorption and enhance PTHLH expression and tumor cell growth (Yin et al., 1999), thus completing a vicious cycle (see diagram). Taken together, PTHLH expression by breast carcinoma cells enhance the development and progression of breast carcinoma metastasis to bone (Guise et al., 1996). Alternatively, cytokines such as IL-8 initiate the process of osteoclastic bone resorption in the early stages of breast cancer metastasis, and PTHLH expression is induced to stimulate the vicious cycle of osteolysis at a later stage (Bendre et al., 2003).
Certain cancer treatments, especially sex steroid hormone deprivation therapies, stimulate bone loss. Bone resorption will result in the release of bone growth factors, which may inadvertently facilitate bone metastasis (Guise, 2000). Treatment with bisphosphonates will prevent bone resorption and reduce the release of bone growth factors (Guise et al., 2005).
Entity Cachexia in hypercalcemia of malignancy
Oncogenesis PTHLH induces a wasting/cachectic syndrome (Iguchi et al., 2001). PTHLH leads to decreased physical activity and lowered energy metabolism independently of the effects of hypercalcemia and proinflammatory cytokines (Onuma et al., 2005). In a rodent model, PTHLH induces a cachectic syndrome (in addition to inducing hypercalcemia of malignancy) by changing the mRNA levels of orexigenic and anorexigenic peptides, except leptin and orexin (Hashimoto et al., 2007). Expression of cachexia-inducing cytokines such as interleukin-6 and leukemia inhibitory factor is increased by PTHLH (Iguchi et al., 2006). Animal data suggest that humanized antibody against PTHLH may be effective for patients with hypercalcemia and cachexia in patients with humoral hypercalcemia of malignancy (Sato et al., 2003).


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Parathyroid hormone-related peptide is a downstream target for ras and src activation.
Li X, Drucker DJ.
J Biol Chem. 1994 Mar 4;269(9):6263-6.
PMID 8119972
Ets2 and protein kinase C epsilon are important regulators of parathyroid hormone-related protein expression in MCF-7 breast cancer cells.
Lindemann RK, Braig M, Hauser CA, Nordheim A, Dittmer J.
Biochem J. 2003 Jun 15;372(Pt 3):787-97.
PMID 12628005
Involvement of parathyroid hormone-related protein in vascular calcification of chronic haemodialysis patients.
Liu F, Fu P, Fan W, Gou R, Huang Y, Qiu H, Zhong H, Huang S.
Nephrology (Carlton). 2012 Aug;17(6):552-60. doi: 10.1111/j.1440-1797.2012.01601.x.
PMID 22448974
Transcriptomic and proteomic analyses in bone tumor cells: Deciphering parathyroid hormone-related protein regulation of the cell cycle and apoptosis.
Mak IW, Turcotte RE, Ghert M.
J Bone Miner Res. 2012 Sep;27(9):1976-91. doi: 10.1002/jbmr.1638.
PMID 22508574
Identification of a cDNA encoding a parathyroid hormone-like peptide from a human tumor associated with humoral hypercalcemia of malignancy.
Mangin M, Webb AC, Dreyer BE, Posillico JT, Ikeda K, Weir EC, Stewart AF, Bander NH, Milstone L, Barton DE, et al.
Proc Natl Acad Sci U S A. 1988 Jan;85(2):597-601.
PMID 2829195
Hypoxia induces PTHrP gene transcription in human cancer cells through the HIF-2a.
Manisterski M, Golan M, Amir S, Weisman Y, Mabjeesh NJ.
Cell Cycle. 2010 Sep 15;9(18):3723-9. Epub 2010 Sep 7.
PMID 20890122
Parathyroid hormone-related protein is an essential growth factor for human clear cell renal carcinoma and a target for the von Hippel-Lindau tumor suppressor gene.
Massfelder T, Lang H, Schordan E, Lindner V, Rothhut S, Welsch S, Simon-Assmann P, Barthelmebs M, Jacqmin D, Helwig JJ.
Cancer Res. 2004 Jan 1;64(1):180-8.
PMID 14729622
Parathyroid hormone-related protein (PTHrP) as a causative factor of cancer-associated wasting: possible involvement of PTHrP in the repression of locomotor activity in rats bearing human tumor xenografts.
Onuma E, Tsunenari T, Saito H, Sato K, Yamada-Okabe H, Ogata E.
Int J Cancer. 2005 Sep 1;116(3):471-8.
PMID 15800941
A midregion parathyroid hormone-related peptide mobilizes cytosolic calcium and stimulates formation of inositol trisphosphate in a squamous carcinoma cell line.
Orloff JJ, Ganz MB, Nathanson MH, Moyer MS, Kats Y, Mitnick M, Behal A, Gasalla-Herraiz J, Isales CM.
Endocrinology. 1996 Dec;137(12):5376-85.
PMID 8940360
Parathyroid hormone-related protein and life expectancy in hypercalcemic cancer patients.
Pecherstorfer M, Schilling T, Blind E, Zimmer-Roth I, Baumgartner G, Ziegler R, Raue F.
J Clin Endocrinol Metab. 1994 May;78(5):1268-70.
PMID 8175989
Localization of parathyroid hormone-related protein in breast cancer metastases: increased incidence in bone compared with other sites.
Powell GJ, Southby J, Danks JA, Stillwell RG, Hayman JA, Henderson MA, Bennett RC, Martin TJ.
Cancer Res. 1991 Jun 1;51(11):3059-61.
PMID 2032246
Regulation of parathyroid hormone-related peptide by estradiol: effect on tumor growth and metastasis in vitro and in vivo.
Rabbani SA, Khalili P, Arakelian A, Pizzi H, Chen G, Goltzman D.
Endocrinology. 2005 Jul;146(7):2885-94. Epub 2005 Apr 14.
PMID 15831570
Treatment of malignancy-associated hypercalcemia and cachexia with humanized anti-parathyroid hormone-related protein antibody.
Sato K, Onuma E, Yocum RC, Ogata E.
Semin Oncol. 2003 Oct;30(5 Suppl 16):167-73. (REVIEW)
PMID 14613038
Alternative splicing of parathyroid hormone-related protein mRNA: expression and stability.
Sellers RS, Luchin AI, Richard V, Brena RM, Lima D, Rosol TJ.
J Mol Endocrinol. 2004 Aug;33(1):227-41.
PMID 15291755
PTH-related protein upregulates integrin alpha6beta4 expression and activates Akt in breast cancer cells.
Shen X, Falzon M.
Exp Cell Res. 2006 Nov 15;312(19):3822-34. Epub 2006 Aug 17.
PMID 16965770
c-myc and skp2 coordinate p27 degradation, vascular smooth muscle proliferation, and neointima formation induced by the parathyroid hormone-related protein.
Sicari BM, Troxell R, Salim F, Tanwir M, Takane KK, Fiaschi-Taesch N.
Endocrinology. 2012 Feb;153(2):861-72. Epub 2011 Dec 30.
PMID 22210745
Alternative promoter usage and mRNA splicing pathways for parathyroid hormone-related protein in normal tissues and tumours.
Southby J, O'Keeffe LM, Martin TJ, Gillespie MT.
Br J Cancer. 1995 Sep;72(3):702-7.
PMID 7669584
Suppression of parathyroid hormone-related protein messenger RNA expression by medroxyprogesterone acetate in breast cancer tissues.
Sugimoto T, Shiba E, Watanabe T, Takai S.
Breast Cancer Res Treat. 1999 Jul;56(1):11-23.
PMID 10517339
A parathyroid hormone-related protein implicated in malignant hypercalcemia: cloning and expression.
Suva LJ, Winslow GA, Wettenhall RE, Hammonds RG, Moseley JM, Diefenbach-Jagger H, Rodda CP, Kemp BE, Rodriguez H, Chen EY, et al.
Science. 1987 Aug 21;237(4817):893-6.
PMID 3616618
Systemic and acute administration of parathyroid hormone-related peptide(1-36) stimulates endogenous beta cell proliferation while preserving function in adult mice.
Williams K, Abanquah D, Joshi-Gokhale S, Otero A, Lin H, Guthalu NK, Zhang X, Mozar A, Bisello A, Stewart AF, Garcia-Ocana A, Vasavada RC.
Diabetologia. 2011 Nov;54(11):2867-77. Epub 2011 Jul 29.
PMID 21800111
Characterization of the human parathyroid hormone-like peptide gene. Functional and evolutionary aspects.
Yasuda T, Banville D, Hendy GN, Goltzman D.
J Biol Chem. 1989 May 5;264(13):7720-5.
PMID 2708388
TGF-beta signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development.
Yin JJ, Selander K, Chirgwin JM, Dallas M, Grubbs BG, Wieser R, Massague J, Mundy GR, Guise TA.
J Clin Invest. 1999 Jan;103(2):197-206.
PMID 9916131
Comparison of the skeletal effects induced by daily administration of PTHrP (1-36) and PTHrP (107-139) to ovariectomized mice.
de Castro LF, Lozano D, Portal-Nunez S, Maycas M, De la Fuente M, Caeiro JR, Esbrit P.
J Cell Physiol. 2012 Apr;227(4):1752-60. doi: 10.1002/jcp.22902.
PMID 21702049
Transient exposure to PTHrP (107-139) exerts anabolic effects through vascular endothelial growth factor receptor 2 in human osteoblastic cells in vitro.
de Gortazar AR, Alonso V, Alvarez-Arroyo MV, Esbrit P.
Calcif Tissue Int. 2006 Nov;79(5):360-9. Epub 2006 Nov 14.
PMID 17120184
The C-terminal region of PTHrP, in addition to the nuclear localization signal, is essential for the intracrine stimulation of proliferation in vascular smooth muscle cells.
de Miguel F, Fiaschi-Taesch N, Lopez-Talavera JC, Takane KK, Massfelder T, Helwig JJ, Stewart AF.
Endocrinology. 2001 Sep;142(9):4096-105.
PMID 11517189


This paper should be referenced as such :
Yeung, SCJ ; Habra, MA
PTHLH (parathyroid hormone-like hormone)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(2):94-101.
Free journal version : [ pdf ]   [ DOI ]
History of this paper:
Yeung, SCJ. PTHLH (parathyroid hormone-like hormone). Atlas Genet Cytogenet Oncol Haematol. 2008;12(3):234-239.

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(12;21)(p11;q22) RUNX1::PTHLH

External links


HGNC (Hugo)PTHLH   9607
Entrez_Gene (NCBI)PTHLH    parathyroid hormone like hormone
AliasesBDE2; HHM; PLP; PTHR; 
GeneCards (Weizmann)PTHLH
Ensembl hg19 (Hinxton)ENSG00000087494 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000087494 [Gene_View]  ENSG00000087494 [Sequence]  chr12:27958084-27969976 [Contig_View]  PTHLH [Vega]
ICGC DataPortalENSG00000087494
Genatlas (Paris)PTHLH
Genetics Home Reference (NIH)PTHLH
Genomic and cartography
GoldenPath hg38 (UCSC)PTHLH  -     chr12:27958084-27969976 -  12p11.22   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PTHLH  -     12p11.22   [Description]    (hg19-Feb_2009)
GoldenPathPTHLH - 12p11.22 [CytoView hg19]  PTHLH - 12p11.22 [CytoView hg38]
Genome Data Viewer NCBIPTHLH [Mapview hg19]  
OMIM168470   613382   
Gene and transcription
Genbank (Entrez)AI569027 AI591151 AI760061 AK313476 BC005961
RefSeq transcript (Entrez)NM_002820 NM_198964 NM_198965 NM_198966
Consensus coding sequences : CCDS (NCBI)PTHLH
Gene Expression Viewer (FireBrowse)PTHLH [ Firebrowse - Broad ]
GenevisibleExpression of PTHLH in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5744
GTEX Portal (Tissue expression)PTHLH
Human Protein AtlasENSG00000087494-PTHLH [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP12272   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP12272  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP12272
Domaine pattern : Prosite (Expaxy)PARATHYROID (PS00335)   
Domains : Interpro (EBI)PTH-rel    PTH/PTH-rel   
Domain families : Pfam (Sanger)Parathyroid (PF01279)   
Domain families : Pfam (NCBI)pfam01279   
Domain families : Smart (EMBL)PTH (SM00087)  
Conserved Domain (NCBI)PTHLH
PDB (RSDB)1BZG    1ET3    1M5N    3FFD    3H3G   
PDB Europe1BZG    1ET3    1M5N    3FFD    3H3G   
PDB (PDBSum)1BZG    1ET3    1M5N    3FFD    3H3G   
PDB (IMB)1BZG    1ET3    1M5N    3FFD    3H3G   
Structural Biology KnowledgeBase1BZG    1ET3    1M5N    3FFD    3H3G   
SCOP (Structural Classification of Proteins)1BZG    1ET3    1M5N    3FFD    3H3G   
CATH (Classification of proteins structures)1BZG    1ET3    1M5N    3FFD    3H3G   
AlphaFold pdb e-kbP12272   
Human Protein Atlas [tissue]ENSG00000087494-PTHLH [tissue]
Protein Interaction databases
IntAct (EBI)P12272
Ontologies - Pathways
Ontology : AmiGOskeletal system development  osteoblast development  negative regulation of inflammatory response to antigenic stimulus  hormone activity  protein binding  extracellular region  extracellular space  nucleoplasm  cytoplasm  Golgi apparatus  cytosol  G protein-coupled receptor signaling pathway  adenylate cyclase-activating G protein-coupled receptor signaling pathway  adenylate cyclase-activating G protein-coupled receptor signaling pathway  cell-cell signaling  female pregnancy  positive regulation of cell population proliferation  negative regulation of cell population proliferation  epidermis development  regulation of gene expression  bone mineralization  regulation of chondrocyte differentiation  negative regulation of chondrocyte differentiation  cAMP metabolic process  peptide hormone receptor binding  peptide hormone receptor binding  negative regulation of chondrocyte development  
Ontology : EGO-EBIskeletal system development  osteoblast development  negative regulation of inflammatory response to antigenic stimulus  hormone activity  protein binding  extracellular region  extracellular space  nucleoplasm  cytoplasm  Golgi apparatus  cytosol  G protein-coupled receptor signaling pathway  adenylate cyclase-activating G protein-coupled receptor signaling pathway  adenylate cyclase-activating G protein-coupled receptor signaling pathway  cell-cell signaling  female pregnancy  positive regulation of cell population proliferation  negative regulation of cell population proliferation  epidermis development  regulation of gene expression  bone mineralization  regulation of chondrocyte differentiation  negative regulation of chondrocyte differentiation  cAMP metabolic process  peptide hormone receptor binding  peptide hormone receptor binding  negative regulation of chondrocyte development  
REACTOMEP12272 [protein]
REACTOME PathwaysR-HSA-418555 [pathway]   
Atlas of Cancer Signalling NetworkPTHLH
Wikipedia pathwaysPTHLH
Orthology - Evolution
GeneTree (enSembl)ENSG00000087494
Phylogenetic Trees/Animal Genes : TreeFamPTHLH
Homologs : HomoloGenePTHLH
Homology/Alignments : Family Browser (UCSC)PTHLH
Gene fusions - Rearrangements
Fusion : QuiverPTHLH
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPTHLH [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PTHLH
Exome Variant ServerPTHLH
GNOMAD BrowserENSG00000087494
Varsome BrowserPTHLH
ACMGPTHLH variants
Genomic Variants (DGV)PTHLH [DGVbeta]
DECIPHERPTHLH [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPTHLH 
ICGC Data PortalPTHLH 
TCGA Data PortalPTHLH 
Broad Tumor PortalPTHLH
OASIS PortalPTHLH [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPTHLH  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DPTHLH
Mutations and Diseases : HGMDPTHLH
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)PTHLH
DoCM (Curated mutations)PTHLH
CIViC (Clinical Interpretations of Variants in Cancer)PTHLH
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM168470    613382   
Genetic Testing Registry PTHLH
NextProtP12272 [Medical]
Target ValidationPTHLH
Huge Navigator PTHLH [HugePedia]
ClinGenPTHLH (curated)
Clinical trials, drugs, therapy
Protein Interactions : CTDPTHLH
Pharm GKB GenePA33952
Clinical trialPTHLH
DataMed IndexPTHLH
PubMed228 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:26:03 CEST 2021

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