DJ-1 binds androgen receptor directly and mediates its activity in hormonally treated prostate cancer cells

Cancer Res. 2007 May 15;67(10):4630-7. doi: 10.1158/0008-5472.CAN-06-4556.

Abstract

The oncogene DJ-1 has been associated with multiple cancers, including prostate cancer, where it can be stabilized by androgens and antiandrogens. However, little data exist on the expression pattern and function of DJ-1 in prostate cancer. To address the function of DJ-1 in prostate, a yeast two-hybrid screen was done to identify novel DJ-1 binding proteins. The androgen receptor (AR) was identified and confirmed as a DJ-1 binding partner. This is the first evidence that DJ-1 directly interacts with AR. We also show that modulation of DJ-1 expression regulated AR transcriptional activity. Importantly, both the subcellular localization of DJ-1 and the interaction with AR are regulated by androgens and antiandrogens. Additionally, immunohistochemical staining on two human prostate cancer tissue arrays was done providing the first large-scale expression analysis of DJ-1 in prostate. DJ-1 expression did not change with Gleason pattern but increased after androgen deprivation therapy, indicating that it may be involved in the development of androgen independence. These data provide a novel mechanism where DJ-1-mediated regulation of AR may promote the progression of prostate cancer to androgen independence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / pharmacology*
  • Androgens / deficiency
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Cell Nucleus / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Neoplasms, Hormone-Dependent / genetics
  • Neoplasms, Hormone-Dependent / metabolism*
  • Neoplasms, Hormone-Dependent / pathology
  • Oncogene Proteins / biosynthesis
  • Oncogene Proteins / metabolism*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Protein Binding
  • Protein Deglycase DJ-1
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Tissue Array Analysis
  • Transcription, Genetic

Substances

  • Androgen Antagonists
  • Androgens
  • Antineoplastic Agents, Hormonal
  • Intracellular Signaling Peptides and Proteins
  • Oncogene Proteins
  • Receptors, Androgen
  • PARK7 protein, human
  • Protein Deglycase DJ-1