The anti-oestrogen fulvestrant (ICI 182,780) reduces the androgen receptor expression, ERK1/2 phosphorylation and cell proliferation in the rat ventral prostate

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dc.contributor.authorFernandes, Sheilla Alessandra Ferreira [UNIFESP]
dc.contributor.authorGomes, Gisele Renata de Oliveira [UNIFESP]
dc.contributor.authorSiu, Erica Rosanna [UNIFESP]
dc.contributor.authorDamas-Souza, Danilo Marchete
dc.contributor.authorBruni-Cardoso, Alexandre
dc.contributor.authorAugusto, Taize Machado
dc.contributor.authorLazari, Maria de Fatima Magalhaes [UNIFESP]
dc.contributor.authorCarvalho, Hernandes Faustino de
dc.contributor.authorPorto, Catarina Segreti [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.date.accessioned2016-01-24T14:17:18Z
dc.date.available2016-01-24T14:17:18Z
dc.date.issued2011-10-01
dc.description.abstractThis study proposed to investigate further the role of oestrogens during pubertal growth of rat ventral prostate, by analysing the effect of anti-oestrogen fulvestrant (ICI 182,780) on the expression of androgen (AR) and oestrogen receptors (ESR1 and ESR2), mitogen-activated protein kinase (ERK1/2) phosphorylation, and expression of Ki-67, a biomarker for cell proliferation. Ventral prostates were obtained from 90-day-old rats treated once a week for 2 months with vehicle (control) or ICI 182,780 (10 mg/rat, s.c.). Transcripts for AR, ESR1 and ESR2 were evaluated by quantitative real-time polymerase chain reaction. Expression of AR, ESR1, ESR2, total and phospho-ERK1/2 was analysed by Western blot or immunofluorescence. Ki-67-positive cells and myosin heavy chain were detected by immunohistochemistry. Cylindrical epithelial cells slightly taller, epithelial dysplasia and an increase in smooth muscle layer were observed in the ventral prostate from ICI 182,780-treated rats. ICI 182,780 did not change the mRNA, but decreased the protein levels for AR in the ventral prostate. the expression of ESR1 (mRNA and protein) was upregulated by ICI 182,780, but no changes were observed on ESR2 expression (mRNA and protein). ICI 182,780 decreased the phosphorylation state of ERK1/2, with no changes in total ERK1/2 levels. Ki-67-positive cells in the ventral prostate were also decreased by ICI 182,780. in conclusion, ICI 182,780 induces downregulation of AR expression and may block the translocation of ESR1 and ESR2 from the nucleus to the plasma membrane, decreasing ERK1/2 phosphorylation and prostatic epithelial cell proliferation. These findings provide a basis for physiological roles of oestrogen in the ventral prostate. Further studies with fulvestrant are necessary in benign prostate hyperplasia and prostatic cancer models.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Pharmacol, Escola Paulista Med, Sect Expt Endocrinol,INFAR, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniv Estadual Campinas, Inst Biol, Dept Anat Cell Biol Physiol & Biophys, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Pharmacol, Escola Paulista Med, Sect Expt Endocrinol,INFAR, BR-04044020 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt
dc.description.sponsorshipIDFAPESP: 2008/56564-1pt
dc.format.extent486-500
dc.identifierhttps://dx.doi.org/10.1111/j.1365-2605.2010.01109.x
dc.identifier.citationInternational Journal of Andrology. Malden: Wiley-Blackwell, v. 34, n. 5, p. 486-500, 2011.
dc.identifier.doi10.1111/j.1365-2605.2010.01109.x
dc.identifier.issn0105-6263
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/34125
dc.identifier.wosWOS:000295269600010
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofInternational Journal of Andrology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectAndrogen receptoren
dc.subjectFulvestranten
dc.subjectOestrogen receptorsen
dc.subjectVentral prostateen
dc.titleThe anti-oestrogen fulvestrant (ICI 182,780) reduces the androgen receptor expression, ERK1/2 phosphorylation and cell proliferation in the rat ventral prostateen
dc.typeinfo:eu-repo/semantics/article
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