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Expression, regulation and function of estrogen receptors in androgen-independent prostate cancer cells PC-3

Grant number: 12/02924-2
Support type:Scholarships in Brazil - Master
Effective date (Start): July 01, 2012
Effective date (End): January 31, 2014
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal Investigator:Catarina Segreti Porto
Grantee:Raisa Pisolato
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:08/56564-1 - Estrogen receptors: expression, regulation, signaling, and function in the male reproductive tract, breast, and brain, AP.TEM

Abstract

Direct and indirect effects of estrogen have been shown in the development and homeostasis of the prostate tissue and in the etiology of prostatic diseases. However, the role of this hormone in the development of castration-resistant prostate cancer (CRPC) is not well established. Estrogen can act via the classical receptors ESR1 (ERalpha) and ESR2 (ERbeta), located predominantly in epithelial and stromal prostate cells, respectively. Early studies also show rapid effects mediated by estrogen receptors GPER and ESR1-36 in breast cancer cells and the possible involvement of these receptors in selective estrogen receptor modulator (SERMs) and antiestrogens resistance. In a previous work we showed, for the first time, the expression of ESR1-36 in the lineage of androgen-independent prostate cancer PC-3. 17²-estradiol acting via classical receptors (ESR1 and ESR2) and / or via receptors involved in fast estrogen action (nongenomic)(GPER and ESR1-36) could play an important role in the progression of CRPC. Therefore, studies of the effects of 17²-estradiol and its receptors may contribute to a better understanding of the mechanisms involved in the progression of prostate cancer and thus to effective therapeutic interventions. This project aims to study the expression, regulation and function of estrogen receptors in androgen-independent prostate cancer cell line PC-3.