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JOURNAL ARTICLES
Prostatic growth and development are regulated by FGF10
A.A. Thomson, G.R. Cunha
Development 1999 126: 3693-3701;

Summary

We have examined the role of Fibroblast Growth Factor 10 (FGF10) during the growth and development of the rat ventral prostate (VP) and seminal vesicle (SV). FGF10 transcripts were abundant at the earliest stages of organ formation and during neonatal organ growth, but were low or absent in growth-quiescent adult organs. In both the VP and SV, FGF10 transcripts were expressed only in a subset of mesenchymal cells and in a pattern consistent with a role as a paracrine epithelial regulator. In the neonatal VP, FGF10 mRNA was expressed initially in mesenchymal cells peripheral to the peri-urethral mesenchyme and distal to the elongating prostatic epithelial buds. At later stages, mesenchymal cells surrounding the epithelial buds also expressed FGF10 transcripts. During induction of the SV, FGF10 mRNA was present in mesenchyme surrounding the lower Wolffian ducts and, at later stages, FGF10 transcripts became restricted to mesenchymal cells subadjacent to the serosa. We investigated whether the FGF10 gene might be regulated by androgens by analysing the levels of FGF10 transcripts in SV and VP organs grown in serum-free organ culture. While FGF10 transcript levels increased after treatment with testosterone in the SV (but not VP), these changes were not sensitive to anti-androgen treatment, and thus it is likely that FGF10 mRNA was not directly regulated by testosterone. Also, FGF10 mRNA was observed in the embryonic female reproductive tract in a position analogous to that of the ventral prostate in males suggesting that FGF10 is not regulated by androgens in vivo. Recombinant FGF10 protein specifically stimulated growth of Dunning epithelial and BPH1 prostatic epithelial cell lines, but had no effect on growth of Dunning stromal cells or primary SV mesenchyme. Furthermore, FGF10 protein stimulated the development of ventral prostate and seminal vesicle organ rudiments in serum-free organ culture. When both FGF10 and testosterone were added to organs in vitro, there was no synergistic induction of development. Additionally, development induced by FGF10 was not inhibited by the addition of the anti-androgen Cyproterone Acetate demonstrating that the effects of FGF10 were not mediated by the androgen receptor. Taken together, our experiments suggest that FGF10 functions as a mesenchymal paracrine regulator of epithelial growth in the prostate and seminal vesicle and that the FGF10 gene is not regulated by androgens

Reference

    1. Alarid E. T.,
    2. Rubin J. S.,
    3. Young P.,
    4. Chedid M.,
    5. Ron D.,
    6. Aaronson S. A.,
    7. Cunha G. R.
    (1994) Keratinocyte growth factor functions in epithelial induction during seminal vesicle development. Proc. Natl. Acad. Sci. USA 91, 1074–1078
    OpenUrlAbstract/FREE Full Text
    1. Bellusci S.,
    2. Grindley J.,
    3. Emoto H.,
    4. Itoh N.,
    5. Hogan B. L. M.
    (1997) Fibroblast Growth Factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung. Development 124, 4867–4878
    OpenUrlAbstract
    1. Culig Z.,
    2. Hobisch A.,
    3. Cronauer M. V.,
    4. Radmayr C.,
    5. Trapman J.,
    6. Hittmair A.,
    7. Bartsch G.,
    8. Klocker H.
    (1994) Androgen receptor activation in prostatic tumor cell lines by insulin-like growth factor-I, keratinocyte growth factor, and epidermal growth factor. Cancer Res 54, 5474–5478
    OpenUrlAbstract/FREE Full Text
    1. Cunha G. R.,
    2. Chung L. W. K.
    (1981) Stromal-epithelial interactions: I. Induction of prostatic phenotype in urothelium of testicular feminized (Tfm/y) mice. J. Steroid Biochem 14, 1317–1321
    OpenUrlCrossRefPubMedWeb of Science
    1. Cunha G. R.,
    2. Donjacour A. A.,
    3. Cooke P. S.,
    4. Mee S.,
    5. Bigsby R. M.,
    6. Higgins S. J.,
    7. Sugimura Y.
    (1987) The endocrinology and developmental biology of the prostate. Endocrine Rev 8, 338–362
    OpenUrlCrossRefPubMedWeb of Science
    1. Donjacour A. A.,
    2. Cunha G. R.
    (1988) The effect of androgen deprivation on branching morphogenesis in the mouse prostate. Dev. Biol 128, 1–14
    OpenUrlCrossRefPubMedWeb of Science
    1. Finch P. W.,
    2. Cunha G. R.,
    3. Rubin J. S.,
    4. Wong J.,
    5. Ron D.
    (1995) Pattern of KGF and KGFR expression during mouse fetal development suggests a role in mediating morphogenetic mesenchymal-epithelial interactions. Dev. Dynamics 203, 223–240
    OpenUrlCrossRefPubMedWeb of Science
    1. Frohman M. A.,
    2. Boyle M.,
    3. Martin G. R.
    (1990). Isolation of the mouse Hox-2.9 gene; analysis of embryonic expression suggests that positional information along the anterior-posterior axis is specified by mesoderm. Development 110, 589–607
    OpenUrlAbstract/FREE Full Text
    1. Guo L.,
    2. Degenstein L.,
    3. Fuchs E.
    (1996) Keratinocyte growth factor is required for hair development but not for wound healing. Genes Dev 10, 165–175
    OpenUrlAbstract/FREE Full Text
    1. Haughney P. C.,
    2. Hayward S. W.,
    3. Dahiya R.,
    4. Cunha G. R.
    (1998) Species-specific detection of growth factor gene expression in developing murine prostatic tissue. Biol. Reprod 59, 93–99
    OpenUrlAbstract/FREE Full Text
    1. Hayward S. W.,
    2. Dahiya R.,
    3. Cunha G. R.,
    4. Bartek J.,
    5. Despande N.,
    6. Narayan P.
    (1995) Establishment and characterization of an immortalized but non-tumorigenic human prostate epithelial cell Line: BPH-1. In Vitro 31, 14–24
    1. Igarashi M.,
    2. Finch P. W.,
    3. Aaronson S. A.
    (1998) Characterization of recombinant human fibroblast growth factor (FGF)-10 reveals functional similarities with keratinocyte growth factor (FGF-7). J. Biol. Chem 273, 13230–13235
    OpenUrlAbstract/FREE Full Text
    1. Lu W.,
    2. Luo Y.,
    3. Kan M.,
    4. McKeehan W. L.
    (1999) Fibroblast growth factor-10. A second candidate stromal to epithelial cell andromedin in prostate. J. Biol. Chem 274, 12827–12834
    OpenUrlAbstract/FREE Full Text
    1. Lung B.,
    2. Cunha G. R.
    (1981) Development of seminal vesicles and coagulating glands in neonatal mice. 1. The morphogenetic effects of various hormonal conditions. Anat. Rec 199, 73–88
    OpenUrlCrossRefPubMed
    1. Mason I. J.,
    2. Pace F. F.,
    3. Smith R.,
    4. Dickson C.
    (1994) FGF-7 (keratinocyte growth factor) expression during mouse development suggests roles in myogenesis, forebrain regionalization and epithelial-mesenchymal interactions. Mech. Dev 15, 15–30
    1. Min H.,
    2. Danilenko D.,
    3. Scully S.,
    4. Bolon B.,
    5. Ring B.,
    6. Tarpley J.,
    7. DeRose M.,
    8. Simonet W.
    (1998) Fgf-10 is required both limb and lung development and exhibits striking functional similarity to Drosophila branchless. Genes Dev 20, 3156–3161
    OpenUrl
    1. Ohuchi H.,
    2. Nakagawa T.,
    3. Yamamoto A.,
    4. Araga A.,
    5. Ohata T.,
    6. Ishimaru Y.,
    7. Yoshioka H.,
    8. Kuwana T.,
    9. Nohno T.,
    10. Yamasaki M.,
    11. et al.
    (1997) The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF8, an apical ectodermal factor. Development 124, 2235–2244
    OpenUrlAbstract
    1. Park W. Y.,
    2. Miranda B.,
    3. Lebeche D.,
    4. Hashimoto G.,
    5. Cardoso W. V.
    (1998) FGF-10 is a chemotactic factor for distal epithelial buds during lung development. Dev. Biol 201, 125–134
    OpenUrlCrossRefPubMedWeb of Science
    1. Peehl D.,
    2. Rubin J.
    (1995) Keratinocyte growth factor: an androgen-regulated mediator of stromal-epithelial interactions in the prostate. World J. of Urology 13, 312–317
    OpenUrlPubMedWeb of Science
    1. Peters K.,
    2. Werner S.,
    3. Liao X.,
    4. Wert S.,
    5. Whitsett J.,
    6. Williams L.
    (1994) Targeted expression of a dominant negative FGF receptor blocksbranching morphogenesis and epithelial differentiation of the mouse lung. EMBO J 12, 973–986
    OpenUrlPubMedWeb of Science
    1. Post M.,
    2. Souza P.,
    3. Liu J.,
    4. Tseu I.,
    5. Wang J.,
    6. Kuliszewski M.,
    7. Tanswell A. K.
    (1996) Keratinocyte growth factor and its receptor are involved in regulating early lung branching. Development 122, 3107–3115
    OpenUrlAbstract
    1. Story M. T.
    (1995) Regulation of prostate growth by fibroblast growth factors. World J. Urol 13, 297–305
    OpenUrlPubMedWeb of Science
    1. Sugimura Y.,
    2. Cunha G. R.,
    3. Donjacour A. A.,
    4. Bigsby R. M.,
    5. Brody J. R.
    (1986) Whole-mount autoradiography study of DNA synthetic activity during postnatal development and androgen-induced regeneration in the mouse prostate. Biol. Reprod 34, 985–995
    OpenUrlAbstract
    1. Sugimura Y.,
    2. Foster B. A.,
    3. Hom Y. K.,
    4. Rubin J. S.,
    5. Finch P. W.,
    6. Aaronson S. A.,
    7. Hayashi N.,
    8. Kawamura J.,
    9. Cunha G. R.
    (1996) Keratinocyte growth factor (KGF) can replace testosterone in the ductal branching morphogenesis of the rat ventral prostate. Int. J. Dev. Biol 40, 941–951
    OpenUrlPubMedWeb of Science
    1. Thomson A. A.,
    2. Foster B. A.,
    3. Cunha G. R.
    (1997) Analysis of growth factor and receptor mRNAs during development of the rat seminal vesicle and prostate. Development 124, 2431–2439
    OpenUrlAbstract
    1. Timms B.,
    2. Lee C.,
    3. Aumuller G.,
    4. Seitz J.
    (1995) Instructive induction of prostate growth and differentiation by a defined urogenital sinus mesenchyme. Microscopy Res. and Technique 30, 319–332
    OpenUrlCrossRefPubMedWeb of Science
    1. Xu X. L.,
    2. Weinstein M.,
    3. Li C. L.,
    4. Naski M.,
    5. Cohen R. I.,
    6. Ornitz D. M.,
    7. Leder P.,
    8. Deng C. X.
    (1998) Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction. Development 125, 753–765
    OpenUrlAbstract
    1. Yamasaki M.,
    2. Miyake A.,
    3. Tagashira S.,
    4. Itoh N.
    (1996) Structure and expression of the rat mRNA encoding a novel member of the fibroblast growth factor family. J. Biol. Chem 271, 15918–15921
    OpenUrlAbstract/FREE Full Text
    1. Yan G.,
    2. Fukabori Y.,
    3. McBride G.,
    4. Nikolaropolous S.,
    5. McKeehan W.
    (1993) Exon switching and activation of stromal and embryonic FGF/FGF receptor genes in prostate epithelial cells accompanies stromal independence and malignancy. Mol. Cell Biol 13, 4513–4522
    OpenUrlAbstract/FREE Full Text
    1. Yan G.,
    2. Fukabori Y.,
    3. Nikolaropoulos S.,
    4. Wang F.,
    5. McKeehan W. L.
    (1992) Heparin-binding keratinocyte growth factor is a candidate stromal to epithelial cell andromedin. Molecular Endocrinology 6, 2123–2128
    OpenUrlCrossRefPubMedWeb of Science
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JOURNAL ARTICLES
Prostatic growth and development are regulated by FGF10
A.A. Thomson, G.R. Cunha
Development 1999 126: 3693-3701;
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