Download or read book Role of Nuclear Receptor Cofactors in Hormone Refractory Prostate Cancer written by and published by . This book was released on 2005 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Previously we discovered that a modest increase in androgen receptor (AR) expression is sufficient and necessary for hormone refractory (HR) prostate cancer progression. Together with published results of common AR overexpression in HR clinical tumor samples, our results indicate that AR overexpression is a cause for HR disease. We also demonstrated that the canonical transcriptional activity of AR is required in this process. Since the AR transcriptional function is mediated by nuclear receptor cofactors, we proposed to study their role in the HR progression. In the first year of study, we proposed to determine if chromatin remodeling or other functions of nuclear receptor cofactors are involved in the HR progression and if coactivators and corepressors are critical in this process. We unexpectedly discovered that blocking deacetylase activities inhibited AR activity, measured by endogenous PSA expression. This is in contrast to published data that deacetylase activities are transcriptionally inhibitory in exogenous reporter systems. We also demonstrated that TRbeta had no squelching effect on AR transcriptional activity, measured by endogenous PSA expression. Finally, we had developed ChIP assay to detect AR and Pol II associated with the PSA promoter.