Beta-catenin affects androgen receptor transcriptional activity and ligand specificity

Abstract

beta-Catenin is a multifunctional molecule with important roles in intercellular adhesion and signal transduction. We reported previously that beta-catenin is mutated in human prostate cancer. In this study, we investigated the role of beta-catenin mutations on androgen receptor (AR) signaling. beta-Catenin significantly enhanced androgen-stimulated transcriptional activation by the AR. beta-Catenin also increased AR transcriptional activation by androstenedione and estradiol and diminished the antagonism of bicalutamide. Coimmunoprecipitation of beta-catenin with AR from LNCaP prostate cancer cells showed that the two molecules are present in the same complex. The amount of beta-catenin in complex with AR was increased by androgen. These findings implicate beta-catenin in the regulation of AR function and support a role for beta-catenin mutations in the pathogenesis of prostate cancer.