β-catenin affects androgen receptor transcriptional activity and ligand specificity

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