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

J Erin Tillman1, Jialing Yuan, Guangyu Gu

  • 1Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232-2765, USA.

Cancer Research
|May 19, 2007
PubMed

Insights

The oncogene DJ-1 interacts with the androgen receptor (AR) in prostate cancer. DJ-1 regulation by hormones may drive cancer progression to androgen independence.

Area of Science:

  • Oncology
  • Molecular Biology
  • Urology

Background:

  • The oncogene DJ-1 is implicated in various cancers.
  • DJ-1 stabilization by androgens and antiandrogens is known in prostate cancer.
  • Limited data exist on DJ-1's role and expression in prostate cancer.

Purpose of the Study:

  • To identify novel DJ-1 binding proteins in prostate cancer.
  • To investigate the functional interaction between DJ-1 and the androgen receptor (AR).
  • To analyze DJ-1 expression patterns in human prostate cancer tissues.

Main Methods:

  • Yeast two-hybrid screening to identify DJ-1 interacting proteins.
  • Confirmation of DJ-1 and AR interaction.
  • Assessment of AR transcriptional activity modulation by DJ-1.
  • Immunohistochemical staining of DJ-1 in human prostate cancer tissue arrays.

Main Results:

  • The androgen receptor (AR) was identified as a novel DJ-1 binding partner.
  • DJ-1 directly interacts with AR, and this interaction is modulated by androgens/antiandrogens.
  • DJ-1 expression increases after androgen deprivation therapy, suggesting a role in androgen independence.
  • DJ-1 expression levels did not correlate with Gleason pattern.

Conclusions:

  • DJ-1 directly interacts with the androgen receptor (AR) in prostate cancer.
  • DJ-1 regulates AR transcriptional activity, with localization and interaction influenced by androgens/antiandrogens.
  • Increased DJ-1 expression post-androgen deprivation suggests a mechanism promoting prostate cancer androgen independence.

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