FGF8 (fibroblast growth factor 8 (androgen-induced))

2011-03-01   Mirjami Mattila , Pirkko Härkönen 

Department of Anatomy, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland

Identity

HGNC
LOCATION
10q24.32
LOCUSID
ALIAS
AIGF,FGF-8,HBGF-8,HH6,KAL6

DNA/RNA

Atlas Image
Figure 1. Exon representation of FGF8 isoforms (modified from Gemel et al., 1996).

Transcription

Alternative splicing of FGF8 gene gives rise to eight potential protein isoforms in the mouse (FGF8a-h) and four in the human (a, b, e, f) (Gemel et al., 1996, see Figure 1).

Proteins

Description

Fibroblast growth factor 8 is a secreted protein mitogen which belongs to fibroblast growth factor family. It exerts its action by binding cell surface tyrosine kinase recetors FGFR1-4 (Powers et al., 2000; Sleeman et al., 2001). It is implicated in embryonic development, tumor growth and angiogenesis. FGF8 was originally found as an androgen-induced growth factor (AIGF) from the conditioned medium of the androgen-dependent mouse mammary carcinoma cell line SC-3 (Tanaka et al., 1992). Whether its expression is directly androgen regulated is not clear (Gnanapragasam et al., 2002; Erdeich-Epstein et al., 2005). However, it has been shown to be co-expressed with androgen receptor in breast and prostate cancer. FGF8 is also called Kal-6 since it belongs to genes which have been shown to be mutated in a subset of patients with Kallmans syndrome (combination of hypogonadotropic hypogonadism and anosmia). In addition, FGF8 belongs to growth factors that could be isolated by affinity chromatography on Heparin-Sepharose columns and are thus called heparin-binding growth factors (HBGF). The interaction of heparin with FGF stabilizes FGF to denaturation (Gospodarowicz and Cheng, 1986) and proteolysis and is required for FGF mediated FGFR activation (Ornitz, 2000).

Expression

In the adult human, FGF8 is expressed in kidney, testis, prostate, breast, peripheral blood leukocytes and in bone marrow (Ghosh et al., 1996; Marsh et al., 1999; Tanaka et al., 1998). However, during embryonal development, its expression is more widely distributed. The expression pattern of FGF8 during mouse embryonal development suggested roles for FGF8 in the morphogenesis of limbs, central nervous system and face, pharyngeal and cardiac systems, and the urogenital organs (Ohuchi et al., 1994; Heikinheimo et al., 1994; Crossley et al., 1996a; Crossley et al., 1996b; Haraguchi et al., 2000). Importantly, FGF8 expression is essential in gastrulation since homozygous loss of FGF8 leads to early embryonic lethality (Sun et al., 1999).
Of the cancer cell lines, FGF8 expression has been detected in LNCaP, DU145, ALVA-31 and PC-3 prostate cancer cell lines, in MCF-7, ZR-75-1, T47-D, MDA-MB-231, SKBR-1, BT-549 and Hs578T breast cancer cell lines (Tanaka et al., 1995; Ghosh et al., 1996; Johnson et al., 1998; Marsh et al., 1999) and in UT-OV-2, UT-OV-4, UT-OV-5, UT-OV-6, UT-OV-10, UT-OV-11 and SK-OV-3 ovarian cancer cell lines (Valve et al., 2000). FGF8 has been shown to be expressed in benign breast and prostate lesions and in breast and prostate cancer (Leung et al., 1996; Tanaka et al., 1998; Dorkin et al., 1999). FGF8 expression is correlated with the expression of androgen receptor in both breast and prostate cancer (Wang et al., 1999; Tanaka et al., 2002). In prostate cancer the expression of FGF8 correlates with the poor prognosis (Dorkin et al., 1999). FGF8b is the primary isoform detected in breast cancer (Marsh et al., 1999) but in prostate cancer in addition to FGF8b, also FGF8a and FGF8e have been detected (Valve et al., 2001). Ovarian cancers of wide variety of histological types express FGF8 and its receptors and increased staining intensity of FGF8 has been associated with loss of differentiation within the tumors (Valve et al., 2000).

Function

FGF receptors, to which FGF8 binds, are transmembrane proteins containing three extracellular immunoglobulin-like domains (IgI, IgII, IgIII), an acidic region between IgI and IgII, a transmembrane domain, and an intracellular tyrosine kinase domain. The involvement of receptor tyrosine phosphorylation in FGF signalling was first suggested by early binding studies (Moscatelli et al., 1987). An important mechanism by which FGF receptors determine specificity for different FGFs is by alternate exon usage of the IgIII forms. The exons coding for the three possible IgIII domains (IgIIIa, IgIIIb, IgIIIc) are situated contiguously and in the same order in FGFR1, FGFR2 and FGFR3 (Johnson et al., 1991; Chellaiah et al., 1994). The FGFR4 gene is unique in that there is only one possible form of its IgIII domain (Vainikka et al., 1992). IgIIIa splice variant codes for a secreted truncated protein which is not capable of transducing signals but instead may act to sequester released FGFs and potentially inhibit FGF signaling. FGF8 predominantly activates c-spliceforms of the receptors which are expressed mainly by the cells of mesenchymal origin. Thus, epithelially secreted FGF8 signals to neighbouring mesenchyme and may have a role in the epithelial-mesenchymal transition important in carcinogenesis. However, FGF8 is also well known as an autocrine growth factor in the stimulation of cancer cell proliferation, anchorage independent growth and migration (Figure 2). Full FGF receptor activation requires a coreceptor, a cell surface heparan sulfate proteoglycan (HSPG), which traps the growth factor on the cell surface and stabilizes the FGF/FGFR complex (Ornitz, 2000). Tissue-specific heparan fragments and tissue specific sulfation patterns of heparans may regulate FGFs by controlling their diffusion in the extracellular matrix and their ability to activate specific receptors (Chang et al., 2000). Strong binding of FGFs to heparin and heparan sulfated proteoglycans leads to deposition and sequestration of secreted or exocytosed FGFs in the extracellular matrix. Storage of FGFs in the extracellular matrix may serve as an angiogenesis regulatory reservoir released in response to degradation of the matrix (Folkman et al., 1988).
FGF activation of FGFRs results in activation of signalling cascades such as phospholipase C gamma, phosphatidiylinositol-3 kinase and MAPK pathways that lead to expression of target genes and increased cell proliferation, survival and migration. Negative modulators of FGF signalling that have been found to be co-expressed with FGF8 include sprouty proteins (Spry1, Spry2), MAP-kinase phosphatase 3 (Mkp3) and Sef (Similar expression to FGFs) genes. Recently, FGF8 has been shown to downregulate the expression of thrombospondin-1 (TSP-1) (Mattila et al., 2006) through two independent pathways, MEK1/MEK2 and PI3K (Tarkkonen et al., 2010). Repression of TSP-1 may be an important mechanism involved in the induction of an angiogenic phenotype and growth of FGF8-expressing cancer.
Atlas Image
Figure 2. Schematic view of the effects of FGF8 on tumor growth and progression. Morphological change in S115 breast cancer cells in vitro (up), induction of angiogenesis in nude mouse S115 tumors (middle, immunohistochemical staining for CD34), increase in nude mouse bone metastasis of MDA-MB-231 breast cancer cells (bottom, x-ray picture).

Homology

FGF8 has 70-80% amino acid sequence identity with FGF17 and FGF18. FGF8, FGF17 and FGF18 form FGF8 subfamily which has similar receptor binding properties and some overlapping sites of expression (Maruoka et al., 1998).

Mutations

Note

Loss-of-function mutations of FGF8 are associated with isolated hypogonadotropic hypogonadism with variable sense of smell (Kallmann syndrome), cleft lip/palate, deafness and flat nasal bridge camplodactyly and hyperlaxity in the human (Trarbach et al., 2010).

Implicated in

Entity name
Breast and prostate cancers
Disease
In humans FGF8 has been shown to be expressed in benign breast and prostate lesions and in breast and prostate cancer (Tanaka et al., 1998; Leung et al., 1996; Dorkin et al., 1999). Furthermore, it has been detected in bone metastases of prostate cancer (Valta et al., 2008). The expression of FGF8 has been shown to be increased in breast cancer when compared to non-malignant breast tissue (Marsh et al., 1999). FGF8 expression is correlated with the expression of androgen receptor in both breast and prostate cancer (Tanaka et al., 2002; Wang et al., 1999).
Prognosis
In prostate cancer the expression of FGF8 correlates with the poor prognosis (Dorkin et al., 1999). FGF8b is the primary isoform detected in breast cancer (Marsh et al., 1999) but in prostate cancer in addition to FGF8b, also FGF8a and FGF8e have been detected (Valve et al., 2001). Interestingly, both FGF8 isoforms a and e are expressed more commonly in prostate cancer than in benign prostate samples used as controls (Valve et al., 2001). Surprisingly, FGF8b, despite of being the most transforming isoform (Ghosh et al., 1996) is expressed in a similar manner in both benign and malignant prostate samples (Valve et al., 2001). The clinical data and experimental evidence strongly suggest that FGF8 has a role in the promotion of growth and progression of hormonal cancers. FGF8 has been shown to function as a potent autocrine growth factor in the stimulation of proliferation of breast and prostate cancer cells. In addition, its paracrine effects in terms of induction of angiogenesis and osteoblastic differentiation may contribute to tumor progression.
Oncogenesis
When transfected to NIH-3T3 cells FGF8 induces anchorage independent growth of the cells and tumorigenesis in nude mice (Kouhara et al., 1994). MMTV-Fgf8 transgenic mice develop mammary and salivary gland neoplasia and ovarian stromal hyperplasia (Daphna-Iken et al., 1998). Targeted expression of FGF8 in transgenic mouse prostate has been shown to result in prostatic intraepithelial neoplasia, stromal hyperplasia and increased inflammation (Song et al., 2002; Elo et al., 2010). Several breast and prostate cancer cell lines transfected with FGF8 have been shown to exhibit increased growth properties. Also morphology and motility of the cells are reportedly altered in response to FGF8 overexpression (Mattila et al., 2001; Ruohola et al., 2001) indicating that FGF8 may affect cytoskeletal and adhesion molecule expression of cancer cells. Similar to FGF2, FGF8 has been shown to have angiogenic potential (Mattila et al., 2001). Increased FGF8 expression is associated with rich vasculature of fast growing tumors (Valta et al., 2008; Valta et al., 2009; Tuomela et al., 2010). As FGF8 has a central role in hormonal cancers which preferentially metastasize to bone, recent studies have focused on the question whether FGF8 has a role in bone metastasis. The first results show that FGF8 is involved in bone metastasis of prostate cancer (Valta et al., 2006; Valta et al., 2008).

Bibliography

Pubmed IDLast YearTitleAuthors
106272882000Differential ability of heparan sulfate proteoglycans to assemble the fibroblast growth factor receptor complex in situ.Chang Z et al
75125691994Fibroblast growth factor receptor (FGFR) 3. Alternative splicing in immunoglobulin-like domain III creates a receptor highly specific for acidic FGF/FGF-1.Chellaiah AT et al
85488161996Roles for FGF8 in the induction, initiation, and maintenance of chick limb development.Crossley PH et al
98409351998MMTV-Fgf8 transgenic mice develop mammary and salivary gland neoplasia and ovarian stromal hyperplasia.Daphna-Iken D et al
106295591999aFGF immunoreactivity in prostate cancer and its co-localization with bFGF and FGF8.Dorkin TJ et al
210766172010Stromal activation associated with development of prostate cancer in prostate-targeted fibroblast growth factor 8b transgenic mice.Elo TD et al
162522612006Androgen inducibility of Fgf8 in Shionogi carcinoma 115 cells correlates with an adjacent t(5;19) translocation.Erdreich-Epstein A et al
86611311996Structure and sequence of human FGF8.Gemel J et al
88913461996Molecular cloning and characterization of human FGF8 alternative messenger RNA forms.Ghosh AK et al
121407572002Regulation of FGF8 expression by the androgen receptor in human prostate cancer.Gnanapragasam VJ et al
35281771986Heparin protects basic and acidic FGF from inactivation.Gospodarowicz D et al
108041872000Molecular analysis of external genitalia formation: the role of fibroblast growth factor (Fgf) genes during genital tubercle formation.Haraguchi R et al
78734031994Fgf-8 expression in the post-gastrulation mouse suggests roles in the development of the face, limbs and central nervous system.Heikinheimo M et al
16520591991The human fibroblast growth factor receptor genes: a common structural arrangement underlies the mechanisms for generating receptor forms that differ in their third immunoglobulin domain.Johnson DE et al
96321411998FGF signaling activates STAT1 and p21 and inhibits the estrogen response and proliferation of MCF-7 cells.Johnson MR et al
82902571994Transforming activity of a newly cloned androgen-induced growth factor.Kouhara H et al
86229051996Over-expression of fibroblast growth factor-8 in human prostate cancer.Leung HY et al
78848991995Fgf-8, activated by proviral insertion, cooperates with the Wnt-1 transgene in murine mammary tumorigenesis.MacArthur CA et al
100236811999Increased expression of fibroblast growth factor 8 in human breast cancer.Marsh SK et al
96515201998Comparison of the expression of three highly related genes, Fgf8, Fgf17 and Fgf18, in the mouse embryo.Maruoka Y et al
167231842006Androgen and fibroblast growth factor 8 (FGF8) downregulation of thrombospondin 1 (TSP1) in mouse breast cancer cells.Mattila MM et al
30329901987High and low affinity binding sites for basic fibroblast growth factor on cultured cells: absence of a role for low affinity binding in the stimulation of plasminogen activator production by bovine capillary endothelial cells.Moscatelli D et al
79805561994Involvement of androgen-induced growth factor (FGF-8) gene in mouse embryogenesis and morphogenesis.Ohuchi H et al
112764322001Fibroblast growth factors.Ornitz DM et al
106550302000FGFs, heparan sulfate and FGFRs: complex interactions essential for development.Ornitz DM et al
87005531996The human FGF-8 gene localizes on chromosome 10q24 and is subjected to induction by androgen in breast cancer cells.Payson RA et al
110219642000Fibroblast growth factors, their receptors and signaling.Powers CJ et al
113588492001Enhanced invasion and tumor growth of fibroblast growth factor 8b-overexpressing MCF-7 human breast cancer cells.Ruohola JK et al
114182382001Identification of a new fibroblast growth factor receptor, FGFR5.Sleeman M et al
111180592000The effect of fibroblast growth factor 8, isoform b, on the biology of prostate carcinoma cells and their interaction with stromal cells.Song Z et al
104216351999Targeted disruption of Fgf8 causes failure of cell migration in the gastrulating mouse embryo.Sun X et al
96057401998High frequency of fibroblast growth factor (FGF) 8 expression in clinical prostate cancers and breast tissues, immunohistochemically demonstrated by a newly established neutralizing monoclonal antibody against FGF 8.Tanaka A et al
124040632002Fibroblast growth factor 8 expression in breast carcinoma: associations with androgen receptor and prostate-specific antigen expressions.Tanaka A et al
77374071995Human androgen-induced growth factor in prostate and breast cancer cells: its molecular cloning and growth properties.Tanaka A et al
204630922010Nonsense mutations in FGF8 gene causing different degrees of human gonadotropin-releasing deficiency.Trarbach EB et al
210345002010Fast growth associated with aberrant vasculature and hypoxia in fibroblast growth factor 8b (FGF8b) over-expressing PC-3 prostate tumour xenografts.Tuomela J et al
13851111992Fibroblast growth factor receptor-4 shows novel features in genomic structure, ligand binding and signal transduction.Vainikka S et al
164394482006Regulation of osteoblast differentiation: a novel function for fibroblast growth factor 8.Valta MP et al
194156852009FGF-8b induces growth and rich vascularization in an orthotopic PC-3 model of prostate cancer.Valta MP et al
110722392000Expression of fibroblast growth factor (FGF)-8 isoforms and FGF receptors in human ovarian tumors.Valve E et al
114066432001Increased expression of FGF-8 isoforms and FGF receptors in human premalignant prostatic intraepithelial neoplasia lesions and prostate cancer.Valve EM et al
103436091999Correlation between androgen receptor expression and FGF8 mRNA levels in patients with prostate cancer and benign prostatic hypertrophy.Wang Q et al

Other Information

Locus ID:

NCBI: 2253
MIM: 600483
HGNC: 3686
Ensembl: ENSG00000107831

Variants:

dbSNP: 2253
ClinVar: 2253
TCGA: ENSG00000107831
COSMIC: FGF8

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000107831ENST00000320185P55075
ENSG00000107831ENST00000344255P55075
ENSG00000107831ENST00000346714P55075
ENSG00000107831ENST00000347978P55075
ENSG00000107831ENST00000469792R4GMQ3
ENSG00000107831ENST00000618991A0A087X1S5

Expression (GTEx)

0
1
2

Pathways

PathwaySourceExternal ID
MAPK signaling pathwayKEGGko04010
Regulation of actin cytoskeletonKEGGko04810
MelanomaKEGGko05218
MAPK signaling pathwayKEGGhsa04010
Regulation of actin cytoskeletonKEGGhsa04810
Pathways in cancerKEGGhsa05200
MelanomaKEGGhsa05218
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
Ras signaling pathwayKEGGhsa04014
Rap1 signaling pathwayKEGGhsa04015
Rap1 signaling pathwayKEGGko04015
DiseaseREACTOMER-HSA-1643685
Diseases of signal transductionREACTOMER-HSA-5663202
Signaling by FGFR in diseaseREACTOMER-HSA-1226099
Signaling by FGFR1 in diseaseREACTOMER-HSA-5655302
FGFR1 mutant receptor activationREACTOMER-HSA-1839124
Signaling by activated point mutants of FGFR1REACTOMER-HSA-1839122
Signaling by FGFR2 in diseaseREACTOMER-HSA-5655253
FGFR2 mutant receptor activationREACTOMER-HSA-1839126
Activated point mutants of FGFR2REACTOMER-HSA-2033519
Signaling by FGFR3 in diseaseREACTOMER-HSA-5655332
FGFR3 mutant receptor activationREACTOMER-HSA-2033514
Signaling by activated point mutants of FGFR3REACTOMER-HSA-1839130
PI3K/AKT Signaling in CancerREACTOMER-HSA-2219528
Constitutive Signaling by Aberrant PI3K in CancerREACTOMER-HSA-2219530
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
Signaling by the B Cell Receptor (BCR)REACTOMER-HSA-983705
Downstream signaling events of B Cell Receptor (BCR)REACTOMER-HSA-1168372
PIP3 activates AKT signalingREACTOMER-HSA-1257604
Negative regulation of the PI3K/AKT networkREACTOMER-HSA-199418
Innate Immune SystemREACTOMER-HSA-168249
DAP12 interactionsREACTOMER-HSA-2172127
DAP12 signalingREACTOMER-HSA-2424491
RAF/MAP kinase cascadeREACTOMER-HSA-5673001
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
FCERI mediated MAPK activationREACTOMER-HSA-2871796
Role of LAT2/NTAL/LAB on calcium mobilizationREACTOMER-HSA-2730905
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-2 signalingREACTOMER-HSA-451927
Interleukin receptor SHC signalingREACTOMER-HSA-912526
Interleukin-3, 5 and GM-CSF signalingREACTOMER-HSA-512988
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
GRB2 events in EGFR signalingREACTOMER-HSA-179812
SHC1 events in EGFR signalingREACTOMER-HSA-180336
GAB1 signalosomeREACTOMER-HSA-180292
Signaling by FGFRREACTOMER-HSA-190236
Signaling by FGFR1REACTOMER-HSA-5654736
FGFR1 ligand binding and activationREACTOMER-HSA-190242
FGFR1c ligand binding and activationREACTOMER-HSA-190373
Downstream signaling of activated FGFR1REACTOMER-HSA-5654687
FRS-mediated FGFR1 signalingREACTOMER-HSA-5654693
Phospholipase C-mediated cascade: FGFR1REACTOMER-HSA-5654219
SHC-mediated cascade:FGFR1REACTOMER-HSA-5654688
PI-3K cascade:FGFR1REACTOMER-HSA-5654689
Negative regulation of FGFR1 signalingREACTOMER-HSA-5654726
Signaling by FGFR2REACTOMER-HSA-5654738
FGFR2 ligand binding and activationREACTOMER-HSA-190241
FGFR2c ligand binding and activationREACTOMER-HSA-190375
Downstream signaling of activated FGFR2REACTOMER-HSA-5654696
FRS-mediated FGFR2 signalingREACTOMER-HSA-5654700
Phospholipase C-mediated cascade; FGFR2REACTOMER-HSA-5654221
SHC-mediated cascade:FGFR2REACTOMER-HSA-5654699
PI-3K cascade:FGFR2REACTOMER-HSA-5654695
Negative regulation of FGFR2 signalingREACTOMER-HSA-5654727
Signaling by FGFR3REACTOMER-HSA-5654741
FGFR3 ligand binding and activationREACTOMER-HSA-190239
FGFR3b ligand binding and activationREACTOMER-HSA-190371
FGFR3c ligand binding and activationREACTOMER-HSA-190372
Downstream signaling of activated FGFR3REACTOMER-HSA-5654708
FRS-mediated FGFR3 signalingREACTOMER-HSA-5654706
Phospholipase C-mediated cascade; FGFR3REACTOMER-HSA-5654227
SHC-mediated cascade:FGFR3REACTOMER-HSA-5654704
PI-3K cascade:FGFR3REACTOMER-HSA-5654710
Negative regulation of FGFR3 signalingREACTOMER-HSA-5654732
Signaling by FGFR4REACTOMER-HSA-5654743
FGFR4 ligand binding and activationREACTOMER-HSA-190322
Downstream signaling of activated FGFR4REACTOMER-HSA-5654716
FRS-mediated FGFR4 signalingREACTOMER-HSA-5654712
Phospholipase C-mediated cascade; FGFR4REACTOMER-HSA-5654228
SHC-mediated cascade:FGFR4REACTOMER-HSA-5654719
PI-3K cascade:FGFR4REACTOMER-HSA-5654720
Negative regulation of FGFR4 signalingREACTOMER-HSA-5654733
Signaling by Insulin receptorREACTOMER-HSA-74752
Insulin receptor signalling cascadeREACTOMER-HSA-74751
IRS-mediated signallingREACTOMER-HSA-112399
PI3K CascadeREACTOMER-HSA-109704
SOS-mediated signallingREACTOMER-HSA-112412
Signalling by NGFREACTOMER-HSA-166520
NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
Signalling to ERKsREACTOMER-HSA-187687
Signalling to RASREACTOMER-HSA-167044
Signalling to p38 via RIT and RINREACTOMER-HSA-187706
Prolonged ERK activation eventsREACTOMER-HSA-169893
Frs2-mediated activationREACTOMER-HSA-170968
ARMS-mediated activationREACTOMER-HSA-170984
PI3K/AKT activationREACTOMER-HSA-198203
Signaling by PDGFREACTOMER-HSA-186797
Downstream signal transductionREACTOMER-HSA-186763
Signaling by VEGFREACTOMER-HSA-194138
VEGFA-VEGFR2 PathwayREACTOMER-HSA-4420097
VEGFR2 mediated cell proliferationREACTOMER-HSA-5218921
Signaling by SCF-KITREACTOMER-HSA-1433557
MAPK family signaling cascadesREACTOMER-HSA-5683057
MAPK1/MAPK3 signalingREACTOMER-HSA-5684996
Signaling by GPCRREACTOMER-HSA-372790
Gastrin-CREB signalling pathway via PKC and MAPKREACTOMER-HSA-881907
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)REACTOMER-HSA-2404192
IGF1R signaling cascadeREACTOMER-HSA-2428924
IRS-related events triggered by IGF1RREACTOMER-HSA-2428928
Signaling by LeptinREACTOMER-HSA-2586552
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
NCAM signaling for neurite out-growthREACTOMER-HSA-375165
PI5P, PP2A and IER3 Regulate PI3K/AKT SignalingREACTOMER-HSA-6811558
FGFRL1 modulation of FGFR1 signalingREACTOMER-HSA-5658623
Signaling by FGFR3 point mutants in cancerREACTOMER-HSA-8853338
RET signalingREACTOMER-HSA-8853659
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224

References

Pubmed IDYearTitleCitations
185969212008Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice.128
163849342006Structural basis by which alternative splicing modulates the organizer activity of FGF8 in the brain.81
213191862011Up-regulation of the fibroblast growth factor 8 subfamily in human hepatocellular carcinoma for cell survival and neoangiogenesis.39
235332282013Prioritizing genetic testing in patients with Kallmann syndrome using clinical phenotypes.33
223190382012Genetic overlap in Kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia.29
183867872008FGF-8 is involved in bone metastasis of prostate cancer.28
218321202011Novel FGF8 mutations associated with recessive holoprosencephaly, craniofacial defects, and hypothalamo-pituitary dysfunction.26
204630922010Nonsense mutations in FGF8 gene causing different degrees of human gonadotropin-releasing deficiency.23
172648672007FGFR2, FGF8, FGF10 and BMP7 as candidate genes for hypospadias.22
172648672007FGFR2, FGF8, FGF10 and BMP7 as candidate genes for hypospadias.22

Citation

Mirjami Mattila ; Pirkko Härkönen

FGF8 (fibroblast growth factor 8 (androgen-induced))

Atlas Genet Cytogenet Oncol Haematol. 2011-03-01

Online version: http://atlasgeneticsoncology.org/gene/40566/fgf8