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Gene Review

FGF8  -  fibroblast growth factor 8 (androgen-induced)

Homo sapiens

Synonyms: AIGF, Androgen-induced growth factor, FGF-8, Fibroblast growth factor 8, HBGF-8, ...
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Disease relevance of FGF8

  • Taken together these data provide first evidence that expression of the mitogen FGF8 in prostate cancer is, at least in part, regulated by the androgen receptor at the transcriptional level [1].
  • In contrast, metastasis was evident in only 10% (1/10) of tumours, which co-expressed both FGF8 and hSef (P<0.001) [2].
  • The sequence variations c.590C>G and c.582-62G>A in FGF8, and, c.550+27C>T, c.727+180T>G, c.830T>C (p.Me186Thr), and c.2454C>T in FGFR2 were found uniquely in patients with hypospadias, as compared with 96 controls [3].
  • The results suggest that forskolin plus FGF8 may contribute to more efficient production of DAergic neurons from human-derived NPCs for therapy of neurodegenerative diseases [4].
  • However, little is known about the FGF8 expression profile in human breast cancer specimens [5].
  • High level of FGF8 expression in tumors is associated with a poor prognosis at least in prostate cancer [6].

High impact information on FGF8

  • These results implicate FGF8 in ensuring tight coordination of the segmentation process and spatiotemporal Hox gene activation [7].
  • Patterning of the anterolateral neural plate (telencephalon) may be regulated by FGF8 produced in the anterior neural ridge [8].
  • An Fgf8 signaling gradient is involved in somite size control [9].
  • En, Fgf8, Pax2 and Pax5, exist in a positive feedback loop for their expression so that mis-expression of any of these genes acts on the feedback loop resulting in induction of the optic tectum in the diencephalon [10].
  • We show that the NC-dependent production of FGF8 in anterior neural ridge is able to restrict Shh expression to the ventral prosencephalon [11].

Chemical compound and disease context of FGF8


Biological context of FGF8


Anatomical context of FGF8

  • Finally, we provide evidence that FGF8 also provides mitogenic stimulation during avian midbrain development [17].
  • Fibroblast growth factors (FGF), and in particular FGF8, have been strongly implicated in prostate carcinogenesis [2].
  • Three alternatively spliced mRNA isoforms of the human fibroblast growth factor-8 (FGF8) gene, expressed in a prostatic carcinoma cell line, have been isolated as cDNA clones and characterized by DNA sequencing [18].
  • Human mesenchymal stem cells isolated from Wharton's jelly of the umbilical cord were induced to transform into dopaminergic neurons in vitro through stepwise culturing in neuron-conditioned medium, sonic hedgehog, and FGF8 [19].
  • In addition, there was no correlation between FGF8 expression and either c-erbB-2 overexpression or the status of the axillary lymph-node metastasis, both of which have been established as important prognostic factors in breast carcinomas [5].

Associations of FGF8 with chemical compounds

  • Finally, using ChIP assays we confirmed in vivo interaction between the AR and the androgen responsive region of the FGF8 promoter [1].
  • Using the 5-stage method, we and others previously demonstrated that Nurr1-overexpressing ES cells, under treatment of signaling molecules such as SHH and FGF8 followed by treatment of ascorbic acid, can differentiate into DA neurons with a high efficiency (> 60% of TH+/Tuj1+ neurons) [20].
  • Different combinations of signals are responsible for different aspects of this early transient induction: FGF initiates expression of Sox3 and ERNI, retinoic acid can induce Cyp26A1 and only a combination of low levels of FGF8 together with Wnt- and BMP-antagonists can induce Otx2 [21].
  • Consistent with this idea, exogenous FGF8 was able to prevent cell death, rescue most of the morphological defects and was able to prevent a decrease in retinoic acid receptorbeta (Rarbeta) expression caused by Citral [22].
  • RESULTS: FGF8 is upregulated in response to TSA treatment along with NF-kappaB transcriptional activity [13].

Regulatory relationships of FGF8

  • In this study, we examined if FGF8 was also regulated by the androgen receptor in human prostate cancer [1].
  • In this cohort, 86% (19/22) of high-grade cancers expressed FGF8 but only 31% (7/22) expressed hSef [2].
  • On the one hand, FGF8 widens beyond the neural folds the competence of the neuroepithelium to develop a RP by inducing the expression of LMX1B and WNT1 [23].
  • These results provide insights into the mechanism by which FGF8 induces an ectopic organizer and suggest that a negative feedback loop between Fgf8 and Otx2 plays a key role in patterning the midbrain and anterior hindbrain [24].
  • FGF8 beads can induce midline properties (e.g. a sulcus) and can modulate the specification and differentiation of adjacent tissues [25].

Other interactions of FGF8

  • Analysis of FGF8 and FGF9 binding to chimeric receptors showed that a broad region spanning Ig domain II and sequences further N-terminal determines binding specificity for these ligands [26].
  • Regulation of FGF8 expression by the androgen receptor in human prostate cancer [1].
  • At sites where cSef is not normally expressed, FGF4 and FGF2, but not FGF8 beads, induced cSef expression [27].
  • Recent studies have demonstrated that some neurons respond also to well-known secreted signaling molecules, best known for their roles as morphogens, such as BMP7, SHH, FGF8, and Wnt [28].
  • In contrast, out of 13 cases of seminoma, immunostaining was negative for FGF8, FGF4, and FGFR1 in 8 cases (61.5%), 6 cases (46.1%), and 7 cases (53.8%), respectively [29].

Analytical, diagnostic and therapeutic context of FGF8


  1. Regulation of FGF8 expression by the androgen receptor in human prostate cancer. Gnanapragasam, V.J., Robson, C.N., Neal, D.E., Leung, H.Y. Oncogene (2002) [Pubmed]
  2. Loss of Sef (similar expression to FGF) expression is associated with high grade and metastatic prostate cancer. Darby, S., Sahadevan, K., Khan, M.M., Robson, C.N., Leung, H.Y., Gnanapragasam, V.J. Oncogene (2006) [Pubmed]
  3. FGFR2, FGF8, FGF10 and BMP7 as candidate genes for hypospadias. Beleza-Meireles, A., Lundberg, F., Lagerstedt, K., Zhou, X., Omrani, D., Frisén, L., Nordenskjöld, A. Eur. J. Hum. Genet. (2007) [Pubmed]
  4. Forskolin cooperating with growth factor on generation of dopaminergic neurons from human fetal mesencephalic neural progenitor cells. Wang, X., Li, X., Wang, K., Zhou, H., Xue, B., Li, L., Wang, X. Neurosci. Lett. (2004) [Pubmed]
  5. Fibroblast growth factor 8 expression in breast carcinoma: associations with androgen receptor and prostate-specific antigen expressions. Tanaka, A., Kamiakito, T., Takayashiki, N., Sakurai, S., Saito, K. Virchows Arch. (2002) [Pubmed]
  6. Role of fibroblast growth factor 8 in growth and progression of hormonal cancer. Mattila, M.M., Härkönen, P.L. Cytokine Growth Factor Rev. (2007) [Pubmed]
  7. FGF signaling controls somite boundary position and regulates segmentation clock control of spatiotemporal Hox gene activation. Dubrulle, J., McGrew, M.J., Pourquié, O. Cell (2001) [Pubmed]
  8. Regionalization of the prosencephalic neural plate. Rubenstein, J.L., Shimamura, K., Martinez, S., Puelles, L. Annu. Rev. Neurosci. (1998) [Pubmed]
  9. Segmentation in vertebrates: clock and gradient finally joined. Aulehla, A., Herrmann, B.G. Genes Dev. (2004) [Pubmed]
  10. Regionalization of the optic tectum: combinations of gene expression that define the tectum. Nakamura, H. Trends Neurosci. (2001) [Pubmed]
  11. The cephalic neural crest exerts a critical effect on forebrain and midbrain development. Creuzet, S.E., Martinez, S., Le Douarin, N.M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  12. The human FGF-8 gene localizes on chromosome 10q24 and is subjected to induction by androgen in breast cancer cells. Payson, R.A., Wu, J., Liu, Y., Chiu, I.M. Oncogene (1996) [Pubmed]
  13. NF-kappaB activation upregulates fibroblast growth factor 8 expression in prostate cancer cells. Armstrong, K., Robson, C.N., Leung, H.Y. Prostate (2006) [Pubmed]
  14. Ectodermal FGFs induce perinodular inhibition of limb chondrogenesis in vitro and in vivo via FGF receptor 2. Moftah, M.Z., Downie, S.A., Bronstein, N.B., Mezentseva, N., Pu, J., Maher, P.A., Newman, S.A. Dev. Biol. (2002) [Pubmed]
  15. FGF8 isoform b expression in human prostate cancer. Gnanapragasam, V.J., Robinson, M.C., Marsh, C., Robson, C.N., Hamdy, F.C., Leung, H.Y. Br. J. Cancer (2003) [Pubmed]
  16. Correlation between androgen receptor expression and FGF8 mRNA levels in patients with prostate cancer and benign prostatic hypertrophy. Wang, Q., Stamp, G.W., Powell, S., Abel, P., Laniado, M., Mahony, C., Lalani, E.N., Waxman, J. J. Clin. Pathol. (1999) [Pubmed]
  17. Sequential roles for Fgf4, En1 and Fgf8 in specification and regionalisation of the midbrain. Shamim, H., Mahmood, R., Logan, C., Doherty, P., Lumsden, A., Mason, I. Development (1999) [Pubmed]
  18. Molecular cloning and characterization of human FGF8 alternative messenger RNA forms. Ghosh, A.K., Shankar, D.B., Shackleford, G.M., Wu, K., T'Ang, A., Miller, G.J., Zheng, J., Roy-Burman, P. Cell Growth Differ. (1996) [Pubmed]
  19. Conversion of human umbilical cord mesenchymal stem cells in Wharton's jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism. Fu, Y.S., Cheng, Y.C., Lin, M.Y., Cheng, H., Chu, P.M., Chou, S.C., Shih, Y.H., Ko, M.H., Sung, M.S. Stem Cells (2006) [Pubmed]
  20. Efficient induction of dopaminergic neurons from embryonic stem cells for application to Parkinson's disease. Kim, D.W. Yonsei Med. J. (2004) [Pubmed]
  21. A role for the hypoblast (AVE) in the initiation of neural induction, independent of its ability to position the primitive streak. Albazerchi, A., Stern, C.D. Dev. Biol. (2007) [Pubmed]
  22. Control of retinoic acid synthesis and FGF expression in the nasal pit is required to pattern the craniofacial skeleton. Song, Y., Hui, J.N., Fu, K.K., Richman, J.M. Dev. Biol. (2004) [Pubmed]
  23. Positive and negative regulations by FGF8 contribute to midbrain roof plate developmental plasticity. Alexandre, P., Bachy, I., Marcou, M., Wassef, M. Development (2006) [Pubmed]
  24. FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expression. Martinez, S., Crossley, P.H., Cobos, I., Rubenstein, J.L., Martin, G.R. Development (1999) [Pubmed]
  25. Coordinate expression of Fgf8, Otx2, Bmp4, and Shh in the rostral prosencephalon during development of the telencephalic and optic vesicles. Crossley, P.H., Martinez, S., Ohkubo, Y., Rubenstein, J.L. Neuroscience (2001) [Pubmed]
  26. Mapping ligand binding domains in chimeric fibroblast growth factor receptor molecules. Multiple regions determine ligand binding specificity. Chellaiah, A., Yuan, W., Chellaiah, M., Ornitz, D.M. J. Biol. Chem. (1999) [Pubmed]
  27. Sef is synexpressed with FGFs during chick embryogenesis and its expression is differentially regulated by FGFs in the developing limb. Harduf, H., Halperin, E., Reshef, R., Ron, D. Dev. Dyn. (2005) [Pubmed]
  28. Morphogen signaling at the vertebrate growth cone: a few cases or a general strategy? Bovolenta, P. J. Neurobiol. (2005) [Pubmed]
  29. Predominant expression of fibroblast growth factor (FGF) 8, FGF4, and FGF receptor 1 in nonseminomatous and highly proliferative components of testicular germ cell tumors. Suzuki, K., Tokue, A., Kamiakito, T., Kuriki, K., Saito, K., Tanaka, A. Virchows Arch. (2001) [Pubmed]
  30. Increased expression of FGF-8 isoforms and FGF receptors in human premalignant prostatic intraepithelial neoplasia lesions and prostate cancer. Valve, E.M., Nevalainen, M.T., Nurmi, M.J., Laato, M.K., Martikainen, P.M., Härkönen, P.L. Lab. Invest. (2001) [Pubmed]
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