Sequential gene expression in response to androgen deprivation: orchestrating secretion activity, proliferation and cell death in the rat ventral prostate

• Grant number: 12/07512-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2012
• End date: August 31, 2016
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Hernandes Faustino de Carvalho
• Grantee: Rafaela da Rosa Ribeiro
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 09/16150-6 - Androgen regulation, sinalization and cellular interactions in prostate development, physiology and regression, AP.TEM
• Associated scholarship(s): 13/23123-0 - The role of MYBL1 and MYBL2 on the androgen-independent prostate cancer cell behavior, BE.EP.DR

Abstract

Androgen deprivation is employed in the therapeutics of prostate cancer because it promotes regressive changes in the organ and tumor. In addition to orchiectomy, many drugs have been designed to achieve similar effects with no need for the surgical removal of the testes and their actions concentrated in androgen blockade. However, little is known about the mechanisms that contribute to prostatic regression, though it is well known that androgens have different effects on promoting proliferation and inhibiting cell death and that epithelial cell apoptosis is independent of the androgen receptor, but relies on the production of death signal or suppression of survival factors by the stromal cells. It is not known what factors are responsible for the progression of androgen-independent prostate cancer, which is more aggressive that the primary cancer. Previously, we have characterized the genes differentially expressed in the rat ventral prostate in response to androgen deprivation and administration of high dose 17b-estradiol (a potent anti-androgen) and found a series of transcription factors that were differentially expressed or enrolled in the regulation of gene networks. Some of these genes are involved with the immediate response (immediate early genes, IEG). In this project we propose to (1) validate the microarray on EVI1, ELK1 (and cFos, cJun e cMyc), HNF4, NFY, GATA2, vMYB, NFkB and c-Rel (2) determine the groups expressed in the prostate epithelium and/or stroma, (3) map the genes regulated by these transcription factors employing functional essays and CHIP-Seq in epithelial and stromal cells, in an attempt to contribute to the elucidation of the mechanisms responsible for the prostate regressive changes in response to castration and the discovery of new therapeutic targes that could improve the effectiveness of the treatment of prostate cancer, in particular the progression to the castration-resistant stage. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

RIBEIRO, Rafaela da Rosa. BMyb and response of prostatic epithelial cells to testosterone levels variations. 2016. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.