Androgen receptor expression is regulated by the phosphoinositide 3-kinase/Akt pathway in normal and tumoral epithelial cells

Biochem J. 2002 Sep 15;366(Pt 3):729-36. doi: 10.1042/BJ20020585.

Abstract

The androgen receptor (AR) is a ligand-responsive transcription factor known to play a central role in the pathogenesis of prostate cancer. However, the regulation of AR gene expression in the normal and pathological prostate remains poorly understood. This study focuses on the effect of the phosphoinositide 3-kinase (PI 3-kinase)/Akt axis on AR expression in vas deferens epithelial cells (VDEC), a suitable model to study androgen regulation of gene expression, and LNCaP cells (derived from a metastasis at the left supraclavicular lymph node from a 50-year-old patient with a confirmed diagnosis of metastatic prostate carcinoma). Taken together, our data show for the first time that the PI 3-kinase/Akt pathway is required for basal and dihydrotestosterone-induced AR protein expression in both VDEC and LNCaP. Inhibition of the PI 3-kinase/Akt pathway reduced AR expression and the decline in AR protein level correlated with a decrease in AR mRNA in VDEC but not in LNCaP. Since PI 3-kinase/Akt axis is active in prostate cancer, cross-talk between PI 3-kinase/Akt and AR signalling pathways may have implications for endocrine therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Cell Differentiation
  • Cell Division
  • Cell Line
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Epithelial Cells / enzymology*
  • Gene Expression Regulation, Enzymologic
  • Humans
  • MAP Kinase Signaling System
  • Male
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation
  • Prostatic Neoplasms / enzymology*
  • Protein Binding
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • RNA / metabolism
  • Receptors, Androgen / metabolism*
  • Signal Transduction
  • Time Factors
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Enzyme Inhibitors
  • Proto-Oncogene Proteins
  • Receptors, Androgen
  • RNA
  • Phosphatidylinositol 3-Kinases
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt