Prostatic Microenvironment In Senescence: Fibroblastic Growth Factors X Hormonal Imbalance

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. © 2013 Springer-Verlag.1415531542Banerjee, S., Banerjee, P.P., Brown, T.R., Castration-induced apoptotic cell death in the Brown Norway rat prostate decreases as a function of age (2000) Endocrinology, 141, pp. 821-822Banerjee, P.P., Banerjee, S., Brown, T.R., Increased androgen receptor expression correlates with development of age-dependent, lobe-specific spontaneous hyperplasia of the Brown Norway rat prostate (2001) Endocrinology, 142 (9), pp. 4066-4075. , DOI 10.1210/en.142.9.4066Carruba, G., Estrogens and mechanisms of prostate cancer progression (2006) Ann N Y Acad Sci, 1089, pp. 201-217Cordeiro, R.S., Scarano, W.R., Campos, S.G., Santos, F.C., Vilamaior, P.S., Góes, R.M., Taboga, S.R., Androgen receptor in the Mongolian gerbil ventral prostate: Evaluation during different phases of postnatal development and following androgen blockage (2008) Micron, 39, pp. 1312-1324Cotton, L.M., O'Bryan, M.K., Hinton, B.T., Cellular signaling by fibroblast growth factors (FGFs) and their receptors (FGFRs) in male reproduction (2008) Endocr Rev, 29, pp. 193-216Culig, Z., Hobisch, A., Cronauer, M.V., Radmayr, C., Trapman, J., Hittmair, A., Bartsch, G., Klocker, H., Androgen receptor activation in prostate tumor cell lines by insulin-like growth factor-I, keratinocyte growth factor, and epidermal growth factor (1994) Cancer Res, 54, pp. 5474-5478Dorkin, T.J., Robinson, M.C., Marsh, C., Bjartell, A., Neal, D.E., Leung, H.Y., FGF8 over-expression in prostate cancer is associated with decreased patient survival and persists in androgen independent disease (1999) Oncogene, 18 (17), pp. 2755-2761. , DOI 10.1038/sj.onc.1202624Ellem, S.J., Risbridger, G.P., The dual, opposing roles of estrogen in the prostate (2009) Ann N Y Acad Sci, 1155, pp. 174-186Gao, J., Arnold, J.T., Isaacs, J.T., Conversion from a paracrine to an autocrine mechanism of androgen-stimulated growth during malignant transformation of prostatic epithelial cells (2001) Cancer Research, 61 (13), pp. 5038-5044Gnanapragasam, V.J., Robinson, M.C., Marsh, C., Robson, C.N., Hamdy, F.C., Leung, H.Y., FGF8 isoform b expression in human prostate cancer (2003) British Journal of Cancer, 88 (9), pp. 1432-1438. , DOI 10.1038/sj.bjc.6600875Heer, R., Collins, A.T., Robson, C.N., Shenton, B.K., Leung, H.Y., KGF suppresses α2β1 integrin function and promotes differentiation of the transient amplifying population in human prostatic epithelium (2006) J Cell Sci, 119, pp. 1416-1424Hetzl, A.C., Montico, F., Lorencini, R.M., Kido, L., Candido, M., Billis, A., Ferreira, U., Cagnon, V.H.A., Fibroblast growth factor, estrogen and prolactin receptor features in different grades of prostatic adenocarcinoma in elderly men (2013) Microsc Res Tech, 76, pp. 321-330Huss, W.J., Barrios, R.J., Foster, B.A., Greenberg, N.M., Differential expression of specific FGF ligand and receptor isoforms during angiogenesis associated with prostate cancer progression (2003) Prostate, 54 (1), pp. 8-16. , DOI 10.1002/pros.10163Ishii, K., Mizokami, A., Tsunoda, T., Heterogenous induction of carcinoma-associated fibroblast-like differentiation in normal human prostatic fibroblasts by co-culturing with prostate cancer cells (2011) J Cell Biochem, 112, pp. 3604-3611Krieg, M., Nass, R., Tunn, S., Effect of aging on endogenous level of 5α-dihydrotestosterone, testosterone, estradiol, and estrone in epithelium and stroma of normal and hyperplastic human prostate (1993) Journal of Clinical Endocrinology and Metabolism, 77 (2), pp. 375-381. , DOI 10.1210/jc.77.2.375Kwabi-Addo, B., Ozen, M., Ittmann, M., The role of fibroblast growth factors and their receptors in prostate cancer (2004) Endocrine-Related Cancer, 11 (4), pp. 709-724. , DOI 10.1677/erc.1.00535Lanner, F., Rossant, J., The role of FGF/Erk signaling in pluripotent cells (2010) Development, 137, pp. 3351-3360Latil, A., Bieche, I., Vidaud, D., Lidereau, R., Berthon, P., Cussenot, O., Vidaud, M., 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 (2001) Cancer Research, 61 (5), pp. 1919-1926Lin, Y., Liu, G., Zhang, Y., Hu, Y.-P., Yu, K., Lin, C., McKeehan, K., Wang, F., Fibroblast growth factor receptor 2 tyrosine kinase is required for prostatic morphogenesis and the acquisition of strict androgen dependency for adult tissue homeostasis (2007) Development, 134 (4), pp. 723-734. , DOI 10.1242/dev.02765Morales, A., Androgen replacement therapy and prostate safety (2002) Eur Urol, 41, pp. 113-120Morrissey, C., Buser, A., Scolaro, J., O'Sullivan, J., Moquin, A., Tenniswood, M., Changes in hormone sensitivity in the ventral prostate of aging Sprague-Dawley rats (2002) Journal of Andrology, 23 (3), pp. 341-351Nemeth, J.A., Zelner, D.J., Lang, S., Lee, C., Keratinocyte growth factor in the rat ventral prostate: Androgen- independent expression (1998) Journal of Endocrinology, 156 (1), pp. 115-125. , DOI 10.1677/joe.0.1560115Planz, B., Wang, Q., Kirley, S.D., Lin, C.-W., Mcdougal, W.S., Androgen responsiveness of stromal cells of the human prostate: Regulation of cell proliferation and keratinocyte growth factor by androgen (1998) Journal of Urology, 160 (5), pp. 1850-1855Prins, G.S., Birch, L., Couse, J.F., Choi, I., Katzenellenbogen, B., Korach, K.S., Estrogen imprinting of the developing prostate gland is mediated through stromal estrogen receptor alpha: Studies with αERKO and βERKO mice (2001) Cancer Research, 61 (16), pp. 6089-6097Roy-Burman, P., Wu, H., Powell, W.C., Hagenkord, J., Cohen, M.B., Genetically defined mouse models that mimic natural aspects of human prostate cancer development (2004) Endocrine-Related Cancer, 11 (2), pp. 225-254. , DOI 10.1677/erc.0.0110225Sattolo, S., Carvalho, C.A.F., Cagnon, V.H.A., Influence of hormonal replacement on the ventral lobe of the prostate of rats (Rattus norvegicus albinus) submitted to chronic ethanol treatment (2004) Tissue and Cell, 36 (6), pp. 417-430. , DOI 10.1016/j.tice.2004.07.004, PII S0040816604000588Scarano, W.R., Vilamaior, P.S.L., Taboga, S.R., Tissue evidence of the testosterone role on the abnormal growth and aging effects reversion in the gerbil (Meriones unguiculatus) prostate (2006) Anatomical Record - Part A Discoveries in Molecular, Cellular, and Evolutionary Biology, 288 (11), pp. 1190-1200. , DOI 10.1002/ar.a.20391Schwertfeger, K., Fibroblast growth factors in development and cancer: Insights for the mammary and prostate glands (2009) Curr Drug Targets, 10, pp. 632-644Shin, J.-H., Kim, H.S., Moon, H.J., Kang, I.H., Kim, T.S., Seok, J.H., Kim, I.Y., Nam, S.Y., Effects of flutamide on puberty in male rats: An evaluation of the protocol for the assessment of pubertal development and thyroid function (2002) Journal of Toxicology and Environmental Health - Part A, 65 (5-6), pp. 433-445. , DOI 10.1080/15287390252808091Smith, P., Rhodes, N.P., Foster, C.S., Upregulation of estrogen and androgen receptors modulate expression of FGF-2 and FGF-7 in human, cultured, prostatic stromal cells exposed to high concentrations of estradiol (2002) Prostate Cancer and Prostatic Diseases, 5 (2), pp. 105-110. , DOI 10.1038/sj.pcan.4500571Tilley, W.D., Horsfall, D.J., McGee, M.A., Effects of ageing and hormonal manipulations on the level of oestrogen receptors in the guinea-pig prostate (1987) Journal of Endocrinology, 112 (1), pp. 139-144Tobin, V.A., Canny, B.J., The regulation of gonadotropin-releasing hormone-induced calcium signals in male rat gonadotrophs by testosterone is mediated by dihydrotestosterone (1998) Endocrinology, 139 (3), pp. 1038-1045. , DOI 10.1210/en.139.3.1038Tomas, D., Kruslin, B., The potential value of (myo)fibroblastic stromal reaction in the diagnosis of prostatic adenocarcinoma (2004) Prostate, 61 (4), pp. 324-331. , DOI 10.1002/pros.20109Valta, M.P., Tuomela, J., Bjartell, A., Valve, E., Vaananen, H.K., Harkonen, P., FGF-8 is involved in bone metastasis of prostate cancer (2008) International Journal of Cancer, 123 (1), pp. 22-31. , DOI 10.1002/ijc.23422Wesche, J., Hagund, K., Haugsten, E.M., Fibroblast growth factors and their receptors in cancer (2011) Biochem J, 437, pp. 199-213Yang, F., Strand, D.W., Rowley, D.R., Fibroblast growth factor-2 mediates transforming growth factor-â action in prostate cancer reactive stroma TGF-â signaling in prostate cancer reactive stroma (2008) Oncogene, 27, pp. 450-459Zar, J.H., (1999) Bioestatistical Analysis, , 4t edn. 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