Beta-catenin affects androgen receptor transcriptional activity and ligand specificity.
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.
Truica
C I
CI
Lombardi Cancer Center, Georgetown University, Washington, DC 20007-2197, USA.
Byers
S
S
Gelmann
E P
EP
D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008024:Ligands; D008297:Male; D009154:Mutation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013379:Substrate Specificity; D015534:Trans-Activators; D015533:Transcriptional Activation / Q000502:physiology*; D014407:Tumor Cells, Cultured; D051176:beta Catenin
D000726:Androgen Antagonists; D000728:Androgens; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D008024:Ligands; D011944:Receptors, Androgen; D015534:Trans-Activators; D051176:beta Catenin