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Prostatic microenvironment in senescence: fibroblastic growth factors × hormonal imbalance

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Abstract

The aim was to characterize and correlate steroid hormone receptors with the FGF2, FGF7 and FGF8 reactivities in the prostatic epithelium and stroma in senile rats. Fifty male senile rats and 10 young male rats were divided into the young (YNG), the senile groups (SE), the castrated group (CAS), the estrogen-deficient group (ED), the castrated + estrogen group (CASE), and the estrogen-deficient + androgen group (EDTEST). The ventral prostate was submitted to immunohistochemical and Western blotting analyses. The results showed decreased AR and ERβ levels and increased ERα in the senile animals in relation to YNG group. Increased ERα and ERβ reactivities presenting differential localization were characterized in the CASE group compared to the CAS group. Increased FGF2 level was observed in the stroma of the CAS and ED groups in relation to the SE group and in the epithelium of the ED group in relation to the other groups. Increased and differential immunolocalization of FGF7 levels were observed in the CAS, ED and CASE groups. The FGF8 levels showed differential localization in the CAS and ED groups compared to the senile group. The intense hormone ablation was favorable to the autocrine signaling of FGF2 and FGF8. FGF7 could be activated in the androgen-independent via considering the increased FGF7 in the castrated rats. We concluded that hormone ablation in senescence was favorable to activation or/and to fibroblast signaling in the prostatic microenvironment.

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References

  • Banerjee S, Banerjee PP, Brown TR (2000) Castration-induced apoptotic cell death in the Brown Norway rat prostate decreases as a function of age. Endocrinology 141:821–822

    CAS  PubMed  Google Scholar 

  • Banerjee PP, Banerjee S, Brown TR (2001) Increased androgen receptor expression correlates with development of age-dependent, lobe-specific spontaneous hyperplasia of the Brown Norway rat prostate. Endocrinology 142:4066–4075

    Article  CAS  PubMed  Google Scholar 

  • Carruba G (2006) Estrogens and mechanisms of prostate cancer progression. Ann N Y Acad Sci 1089:201–217

    Article  CAS  PubMed  Google Scholar 

  • Cordeiro RS, Scarano WR, Campos SG, Santos FC, Vilamaior PS, Góes RM, Taboga SR (2008) Androgen receptor in the Mongolian gerbil ventral prostate: Evaluation during different phases of postnatal development and following androgen blockage. Micron 39:1312–1324

    Article  CAS  PubMed  Google Scholar 

  • Cotton LM, O’bryan MK, Hinton BT (2008) Cellular signaling by fibroblast growth factors (FGFs) and their receptors (FGFRs) in male reproduction. Endocr Rev 29:193–216

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Culig Z, Hobisch A, Cronauer MV, Radmayr C, Trapman J, Hittmair A, Bartsch G, Klocker H (1994) Androgen receptor activation in prostate tumor cell lines by insulin-like growth factor-I, keratinocyte growth factor, and epidermal growth factor. Cancer Res 54:5474–5478

    CAS  PubMed  Google Scholar 

  • Dorkin TJ, Robinson MC, Marsh C et al (1999) FGF8 over-expression in prostate cancer is associated with decreased patient survival and persists in androgen independent disease. Oncongene 18:2755–2761

    Article  CAS  Google Scholar 

  • Ellem SJ, Risbridger GP (2009) The dual, opposing roles of estrogen in the prostate. Ann N Y Acad Sci 1155:174–186

    Article  CAS  PubMed  Google Scholar 

  • Gao J, Arnold JT, Isaacs JT (2001) Conversion from a paracrine to an autocrine mechanism of androgen-stimulated growth during malignant transformation of prostatic epithelial cells. Cancer Res 61:5038–5044

    CAS  PubMed  Google Scholar 

  • Gnanapragasam VJ, Robinson MC, Marsh C et al (2003) FGF8 isoform b expression in human prostate cancer. Br J Cancer 88:1432–1438

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Heer R, Collins AT, Robson CN, Shenton BK, Leung HY (2006) KGF suppresses α2β1 integrin function and promotes differentiation of the transient amplifying population in human prostatic epithelium. J Cell Sci 119:1416–1424

    Article  CAS  PubMed  Google Scholar 

  • Hetzl AC, Montico F, Lorencini RM, Kido L, Candido M, Billis A, Ferreira U, Cagnon VHA (2013) Fibroblast growth factor, estrogen and prolactin receptor features in different grades of prostatic adenocarcinoma in elderly men. Microsc Res Tech 76:321–330

    Google Scholar 

  • Huss WJ, Barrios RJ, Foster BA, Greenberg NM (2003) Differential expression of specific FGF ligand and receptor isoforms during angiogenesis associated with prostate cancer progression. Prostate 54:8–16

    Article  CAS  PubMed  Google Scholar 

  • Ishii K, Mizokami A, Tsunoda T et al (2011) Heterogenous induction of carcinoma-associated fibroblast-like differentiation in normal human prostatic fibroblasts by co-culturing with prostate cancer cells. J Cell Biochem 112:3604–3611

    Article  CAS  PubMed  Google Scholar 

  • Krieg M, Nass R, Tunn S (1993) Effect of aging on endogenous level of 5 α-dihydrotestosterone, testosterone, estradiol, and estrone in epithelium and stroma of normal and hyperplastic human prostate. J Clin Endocrinol Metab 77:375–381

    CAS  PubMed  Google Scholar 

  • Kwabi-Addo B, Ozen M, Ittmann M (2004) The role of fibroblast growth factors and their receptors in prostate cancer. Endocr Relat Cancer 11:709–724

    Article  CAS  PubMed  Google Scholar 

  • Lanner F, Rossant J (2010) The role of FGF/Erk signaling in pluripotent cells. Development 137:3351–3360

    Article  CAS  PubMed  Google Scholar 

  • Latil A, Bieche I, Vidaud D et al (2001) Evaluation of androgen, estrogen (ERα and ERβ), and progesterone receptor expression in human prostate cancer by real-time quantitative reverse transcription-polymerase chain reaction assays. Cancer Res 60:1919–1926

    Google Scholar 

  • Lin Y, Liu G, Zhang Y et al (2007) Fibroblast growth factor receptor 2 tyrosine kinase is required for prostatic morphogenesis and the acquisition of strict androgen dependency for adult tissue homeostasis. Development 134:723–734

    Article  CAS  PubMed  Google Scholar 

  • Morales A (2002) Androgen replacement therapy and prostate safety. Eur Urol 41:113–120

    Article  CAS  PubMed  Google Scholar 

  • Morrissey C, Buser A, Sscolaro J, O’sullivan J, Moquin A, Tenniswood M (2002) Changes in hormone sensitivity in the ventral prostate of aging Sprague–Dawley rats. J Androl 23:341–351

    CAS  PubMed  Google Scholar 

  • Nemeth JA, Zelnen DL, Lang S et al (1998) Keratinocyte growth factor in the rat ventral prostate: androgen-independent expression. J Endocrinol 156:115–125

    Article  CAS  PubMed  Google Scholar 

  • Planz B, Wang Q, Kirley SD, Lin CW, McDougal WS (1998) Androgen responsiveness of stromal cells of the human prostate: regulation of cell proliferation and keratinocyte growth factor by androgen. J Urol 160:1850–1855

    Article  CAS  PubMed  Google Scholar 

  • Prins GS, Birch L, Couse JF, Choi I, Katzenellenbogen B, Korach KS (2001) Estrogen imprinting of the developing prostate gland is mediated through stromal estrogen receptor alpha: studies with αERKO and βERKO mice. Cancer Res 61:6089–6097

    CAS  PubMed  Google Scholar 

  • Roy-Burman P, Wu H, Powell WC, Hagenkord J, Cohen MB (2004) Genetically defined mouse models that mimic natural aspects of human prostate cancer development. Endocr Relat Cancer 11:225–254

    Article  CAS  PubMed  Google Scholar 

  • Sáttolo S, Carvalho CAF, Cagnon VHA (2004) Influence of hormonal replacement on the ventral lobe of the prostate of rats (Rattus norvegicus albinus) submitted to chronic ethanol treatment. Tissue Cell 36:417–430

    Article  CAS  PubMed  Google Scholar 

  • Scarano WR, Vilamaior PSL, Taboga SR (2006) Tissue evidence of the testosterone role on the abnormal growth and aging effects reversion in the gerbil (Meriones unguiculatus) prostate. Anat Rec A 288:1190–1200

    Article  CAS  Google Scholar 

  • Schwertfeger K (2009) Fibroblast growth factors in development and cancer: insights for the mammary and prostate glands. Curr Drug Targets 10:632–644

    Article  CAS  PubMed  Google Scholar 

  • Shin JH, Kim HS, Moon HJ, Kang H, Kim TS, Seok JH, Kim IY, Park KL, Han SY, Nam SY (2002) Effects of flutamide on puberty in male rats: an evaluation of the protocol for the assessment of pubertal development and thyroid function. J Toxicol Environ Health A 65:433–445

    Article  CAS  PubMed  Google Scholar 

  • Smith P, Rhodes NP, Ke Y, Foster CS (2002) Upregulation of estrogen and androgen receptors modulate expression of FGF-2 and FGF-7 in human, cultured, prostatic stromal cells exposed to high concentration of estradiol. Prostate Cancer Prostatic Dis 5:105–110

    Article  CAS  PubMed  Google Scholar 

  • Tilley WD, Horsfall DJ, Mcgee MA, Alderman JE, Marshall VR (1987) Effects of ageing and hormonal manipulations on the level of oestrogen receptors in the guinea-pig prostate. J Endocrinol 112:139–144

    Article  CAS  PubMed  Google Scholar 

  • Tobin VA, Canny BJ (1998) The regulation of gonadotropin-releasing hormone-induced calcium signals in male rat gonadotrophs by testosterone is mediated by dihydrotestosterone. Endocrinology 139:1038–1045

    CAS  PubMed  Google Scholar 

  • Tomas D, Kruslin B (2004) The potential value of (myo) fibroblastic stromal reaction in the diagnosis of prostatic adenocarcinoma. Prostate 61:324–331

    Article  PubMed  Google Scholar 

  • Valta MP, Tuomela J, Bjartell A et al (2008) FGF-8 is involved in bone metastasis of prostate cancer. Int J Cancer 123:22–31

    Article  CAS  PubMed  Google Scholar 

  • Wesche J, Hagund K, Haugsten EM (2011) Fibroblast growth factors and their receptors in cancer. Biochem J 437:199–213

    Article  CAS  PubMed  Google Scholar 

  • Yang F, Strand DW, Rowley DR (2008) Fibroblast growth factor-2 mediates transforming growth factor-β action in prostate cancer reactive stroma TGF-β signaling in prostate cancer reactive stroma. Oncogene 27:450–459

    Article  CAS  PubMed  Google Scholar 

  • Zar JH (1999) Bioestatistical analysis, 4t edn. Prentice Hall Upper, New Jersey

    Google Scholar 

Download references

Acknowledgments

This work was supported by São Paulo Research Foundation (2010/01739-1 and 2009/50396-2).

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Authors and Affiliations

  1. Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), P.O. Box 6109, Campinas, SP, 13083-865, Brazil

    A. C. Hetzl, F. Montico, R. M. Lorencini, L. A. Kido, E. M. Cândido & V. H. A. Cagnon

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  1. A. C. Hetzl
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  2. F. Montico
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  3. R. M. Lorencini
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  4. L. A. Kido
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  5. E. M. Cândido
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  6. V. H. A. Cagnon
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Correspondence to V. H. A. Cagnon.

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Hetzl, A.C., Montico, F., Lorencini, R.M. et al. Prostatic microenvironment in senescence: fibroblastic growth factors × hormonal imbalance. Histochem Cell Biol 141, 531–542 (2014). https://doi.org/10.1007/s00418-013-1173-y

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  • DOI: https://doi.org/10.1007/s00418-013-1173-y

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