b-Catenin Affects Androgen Receptor Transcriptional Activity and Ligand Specificity

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