The androgen receptor can promote beta-catenin nuclear translocation independently of adenomatous polyposis coli

J Biol Chem. 2002 May 17;277(20):17933-43. doi: 10.1074/jbc.M200135200. Epub 2002 Feb 20.

Abstract

We provide evidence that the androgen receptor (AR) can promote nuclear translocation of beta-catenin in LNCaP and PC3 prostate cancer cells. Using AR-expressing cells (LNCaP) and non-AR-expressing cells (PC3) we showed by time course cell fractionation that the AR can shuttle beta-catenin into the nucleus when exposed to exogenous androgen. Cells exposed to the synthetic androgen, R1881, show distinct, punctate, nuclear co-localization of the AR and beta-catenin. We further showed that the AR does not interact with adenomatous polyposis coli or glycogen synthase kinase-3beta and, therefore, conclude that androgen-mediated transport of beta-catenin occurs through a distinct pathway. The minimal necessary components of the AR and beta-catenin required for binding nuclear accumulation of beta-catenin nuclear import appears to be the DNA/ligand binding regions and the Armadillo repeats of beta-catenin. We also employed a novel DNA binding assay to illustrate that beta-catenin has the capacity to bind to the probasin promoter in an AR-dependent manner. The physiological relevance of AR-mediated transport of beta-catenin and binding to an AR promoter appeared to be a substantial increase in AR transcriptional reporter activity. AR-mediated import represents a novel mode of nuclear accumulation of beta-catenin.

MeSH terms

  • Active Transport, Cell Nucleus
  • Adenomatous Polyposis Coli / metabolism*
  • Androgen-Binding Protein / genetics
  • Androgen-Binding Protein / metabolism
  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cell Nucleus / metabolism*
  • Cytoskeletal Proteins / metabolism*
  • DNA / metabolism
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinases
  • Humans
  • Male
  • Metribolone / metabolism
  • Promoter Regions, Genetic
  • Prostatic Neoplasms / metabolism
  • Receptors, Androgen / metabolism*
  • Trans-Activators*
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • beta Catenin

Substances

  • Androgen-Binding Protein
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Receptors, Androgen
  • Trans-Activators
  • beta Catenin
  • probasin
  • Metribolone
  • DNA
  • Glycogen Synthase Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Glycogen Synthase Kinase 3