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Oncogene
  • Original Paper
  • Published:

Regulation of FGF8 expression by the androgen receptor in human prostate cancer

Oncogenevolume 21, pages5069–5080 (2002)Cite this article

Abstract

Fibroblast growth factor 8 (FGF8) has been shown to play a key role in prostate carcinogenesis. It was initially cloned as an androgen induced protein in mouse mammary cancer SC3 cells. In this study, we examined if FGF8 was also regulated by the androgen receptor in human prostate cancer. FGF8b protein expression in resected clinical prostate cancer correlated closely with expression of the androgen receptor (AR). In the androgen sensitive CWR22 prostate xenograft, we observed up-regulation of FGF8b immunoreactivity in testosterone supplemented mice while castration markedly reduced its signal. Furthermore, FGF8b protein expression in AR positive LNCaP cells was similarly enhanced by androgens. The proximal promoter of the humanFGF8 gene was cloned into a luciferase reporter construct (FGF8.luc). FGF8.luc activity in AR positive LNCaP and SC3 cells was increased 2.5-fold by androgens. In AR negative DU145 cells, maximal induction of FGF8.luc required both co-transfection of the AR and the presence of androgens. The anti-androgen bicalutamide completely abolished AR mediated FGF8.luc induction. Deletion constructs from FGF8.luc have further defined an active promoter region and an androgen responsive region. Nucleotide analysis of this androgen responsive region has revealed putative androgen response elements. Finally, using ChIP assays we confirmedin vivo interaction between the AR and the androgen responsive region of theFGF8 promoter. 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.

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Abbreviations

AR:

androgen receptor

ARE:

androgen response element

FGF8:

fibroblast growth factor 8

ChIP:

chromatin immunoprecipitation

CWR22:

Case Western Reserve Prostate Xenograft strain 22

MMTV:

mouse mammary tumour virus

PCR:

polymerase chain reaction

PSA:

prostate specific antigen

SHR:

steroid hormone receptor

References

  • Bower M, Waxman J . 1997Sem. Cancer Biol.8: 3–9

  • Brady ME, Ozanne DM, Gaughan L, Waite I, Cook S, Neal DE, Robson CN . 1999J. Biol. Chem.274: 17599–17604

  • Claessens F, Verrijdt G, Schoenmaker E, Haelens A, Peeters B, Verhoven G, Rombauts W . 2001J. Steroid Biochem. Mol. Biol.76: 23–30

  • Crossley PH, Minowada G, MacArthur CA, Martin GR . 1996Cell84: 127–136

  • Daphna-Iken D, Shankar DB, Lawshwe A, Ornitz DM, Shackleford GM, MacArthur CA . 1998Oncogene17: 2711–2717

  • De Vere White RW, Meyers F, Chi SG, Chamberlain S, Siders D, Lee F, Stewart S, Gumerlock PH . 1997Eur. Urol.31: 1–6

  • Dorkin TJ, Robinson MR, Marsh C, Bjartell A, Neal DE, Leung HY . 1999Oncogene18: 2755–2761

  • Gemel J, Gorry M, Ehrlich GD, MacArthur CA . 1996Genomics35: 253–257

  • Gemel J, Jacobsen C, MacArthur C . 1999J. Biol. Chem.274: 6020–6026

  • Ghosh AK, Shankar DB, Shakleford GM, Wu K, T'Ang A, Miller GJ, Zheng J, Roy-Burman P . 1996Cell Growth Diff.7: 1425–1434

  • Glass CK, Rose DW, Rosenfeld MG . 1997Curr. Opin. Cell. Biol.9: 222–232

  • Gnanapragasam VJ, Leung HY, Pulimood AS, Neal DE, Robson CN . 2001Br. J. Cancer85: 1928–1936

  • Greenlee RT, Murray T, Bolden S, Wingo PA . 2000Can. J. Clin.50: 7–33

  • Horwitz KB, Jackson TA, Bain DL, Richer JK, Takimoto GS, Tung LS . 1996Mol. Endocrinology10: 1167–1177

  • Ittman M, Mansukhani A . 1997J. Urol.157: 351–356

  • Kapoun AM, Shackleford GM . 1997Oncogene14: 2985–2989

  • Koivisto PA, Helin HJ . 1999J. Pathol.189: 219–223

  • Kouhara H, Koga M, Kasayama S, Tanaka A, Kishimoto T, Sato B . 1994Oncogene9: 455–462

  • Kuriki K, Kamiakito T, Yoshida H, Saito K, Fukayama M, Tanaka A . 2000Cell Mol. Biol.46: 1147–1156

  • Lee SM, Danielian PS, Fritzsch B, McMahon AP . 1997Development124: 959–969

  • Leung HY, Dickson C, Robson CN, Neal DE . 1996Oncogene12: 1833–1835

  • MacArthur CA, Lawshe A, Shankar DB, Heikinheimo M, Shackleford GM . 1995Cell Growth Diff.6: 817–825

  • Merril RM, Potosky AL, Feuer EJ . 1996J. Natl. Can. Inst.88: 1683–1685

  • Myers RB, Oeschlager DK, Coan PN, Frost AR, Weiss HL, Manne U, Pretlow TG, Grizzle WE . 1999J. Urol.161: 945–949

  • Murtha P, Tindall DJ, Young CY . 1993Biochemistry32: 6459–6464

  • Riegman PH, Vlietstra RJ, van der Korput J, Brinkmann AO, Trapman J . 1991Mol. Endocrinology5: 1921–1930

  • Roche PJ, Hoare S, Parker MG . 1992Mol. Endocrinology6: 2229–2235

  • Rudra-Ganguly N, Zheng J, Hoang AT, Roy-Burman P . 1998Oncogene16: 1487–1492

  • Schmitt FJ, Hearn MT, Risbridger GP . 1996J. Steroid Biochem. Mol. Biol.57: 173–178

  • Smith CL, Onate SA, Tsai MJ, McDonnel PD, O'Malley BW . 1996Proc. Natl. Acad. Sci. USA93: 8884–8888

  • Song Z, Powell W, Kasahara N, Van Bokhoven A, Miller G, Roy-Burman P . 2000Cancer Res.60: 6730–6736

  • Story MT, Hopp KA, Molter M, Meier DA . 1994Growth Factors10: 269–280

  • Tanaka A, Miyamoto K, Minamino N, Takeda M, Sato B, Matsuo H, Matsumoto K . 1992Proc. Natl. Acad. Sci. USA89: 8928–8932

  • Tanaka A, Furuya A, Yamasaki M, Hanai N, Kuriki K, Kamiakito T, Kobayashi Y, Yoshida H, Koike M, Fukuyama M . 1998Cancer Res.58: 2053–2056

  • Tanaka S, Ueo H, Mafune K, Mori M, Wands JR, Sugimachi K . 2001Dig. Dis. and Sci.46: 1016–1021

  • Valve EM, Tasanen MJ, Ruohola JK, Harkonen PL . 1998Biochem. and Biophys. Res. Comm.250: 805–808

  • Valve EM, Nevalainen MT, Nurmi MJ, Laato MK, Martikainen PM, Harkonen PL . 2001Lab. Invest.81: 815–826

  • Van der Kwast T, Schalken J, Ruizveld de Winter J, van Vroonhoven C, Mulder E, Boersma W, Trapman J . 1991Int. J. Cancer48: 189–193

  • Wainstein MA, He F, Robinson D, Kung HJ, Schwartz S, Giaconia JM, Edgehouse NL, Pretlow TG, Bodner DR, Kursh ED . 1994Cancer Res.54: 6049–6052

  • Wang Q, Stamp GW, Powell S, Abel P, Laniado M, Mahony C, Lalani EN, Waxman J . 1999J. Clin. Pathol.52: 29–34

  • Wu J, Payson RA, Lang JC, Chiu IM . 1997J. Steroid Biochem. Mol. Biol.62: 1–10

  • Yeh S, Chang C . 1996Proc. Natl. Acad. Sci. USA93: 5517–5521

  • Yoshiura K, Leysens NJ, Chang J, Ward D, Murray JC, Muenke M . 1997Am. J. Med. Gen.72: 354–362

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Acknowledgements

This project was funded by the Cancer Research Campaign of the UK, grant no SP2503/0101. We thank Dr Clive Dickson (Imperial Cancer Research Fund, London, UK) for the human FGF8 genomic clone, Professor TG Pretlow (Case Western Reserve University, Cleveland, Ohio, USA) for the CWR22 cells, Professor DR Newell (Cancer Research Unit, University of Newcastle-upon-Tyne) for assistance with the animal studies. We thank Susan Cook and Louise McCarthy for expert technical assistance.

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Authors and Affiliations

  1. Prostate Research Group, School of Surgical Sciences, University of Newcastle-upon-Tyne, Framlington Place, Newcastle-upon-Tyne, NE2 4HH, UK

    Vincent J Gnanapragasam, Craig N Robson, David E Neal & Hing Y Leung

Authors
  1. Vincent J Gnanapragasam
  2. Craig N Robson
  3. David E Neal
  4. Hing Y Leung

Corresponding author

Correspondence toHing Y Leung.

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Gnanapragasam, V., Robson, C., Neal, D.et al. Regulation of FGF8 expression by the androgen receptor in human prostate cancer.Oncogene21, 5069–5080 (2002). https://doi.org/10.1038/sj.onc.1205663

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