Beta-catenin affects androgen receptor transcriptional activity and ligand specificity

Cancer Res. 2000 Sep 1;60(17):4709-13.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androgen Antagonists / pharmacology
  • Androgens / physiology
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Cytoskeletal Proteins / physiology*
  • Humans
  • Ligands
  • Male
  • Mutation
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Receptors, Androgen / physiology*
  • Substrate Specificity
  • Trans-Activators*
  • Transcriptional Activation / physiology*
  • Tumor Cells, Cultured
  • beta Catenin

Substances

  • Androgen Antagonists
  • Androgens
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Ligands
  • Receptors, Androgen
  • Trans-Activators
  • beta Catenin