RWPE-1 cells: correlation between the expression of p63 and the androgen receptor (AR)

• Grant number: 14/23528-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2015
• End date: September 30, 2015
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Hernandes Faustino de Carvalho
• Grantee: Leonardo de Oliveira Mendes
• 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

Abstract

Prostate develops from p63-positive cells of the urogenital sinus epithelium. P63 knock out mouse develops no prostate. P63 expression is kept at the distal epithelial tip of the growing prostate and in basal cells along the epithelial structures in the full developed gland. Prostate induction occurs in the presence of androgens and takes place in response to paracrine factors produced by the stromal cell in the urogenital sinus mesenchyme, which express the androgen receptor (AR), while the epithelium itself does not express this nuclear receptor. In this sense, prostate induction and the possible differentiation of luminal secretory cells from basal cells involve the inhibition of p63 and activation of AR expression. RWPE-1 cells represent an excellent model for the study of prostate induction. Sup-populations express either p63 or AR under normal culture conditions. These cells express PSA when stimulated by laminin (Matrigel), and it is well known that PSA expression is highly dependent on AR activation. In this project, we will investigate aspects of the reciprocal regulation of p63 and AR in RWPE-1 cells. After showing the expression of the AR, we will determine how it interacts with promoter region of the P63 gene and how p63 interacts with the AR promoter. We will use bioinformatics to determine the distribution of conserved transcription factor binding sites and chromatin immunoprecipitation to determine the physical interaction of the two transcription factors with the promoter (and/or enhancer) region of the other gene. In addition, we will start to characterize the possible signaling pathway leading from laminina stimulation to gene expression at the level of transcription.