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DJ-1 Binds Androgen Receptor Directly and Mediates Its Activity in Hormonally Treated Prostate Cancer Cells

Departments of ¹ Urologic Surgery and ² Cancer Biology, Vanderbilt University Medical Center; ³ Department of Biological Sciences, Vanderbilt University; ⁴ The Vanderbilt-Ingram Cancer Center, Nashville, Tennessee; ⁵ The Prostate Centre, University of British Columbia; and ⁶ Vancouver General Hospital, Vancouver, British Columbia, Canada

Requests for reprints: Susan Kasper, Department of Urologic Surgery, A-1302 Medical Center North, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, TN 37232-2765. Phone: 615-343-5921; E-mail: susan.kasper{at}vanderbilt.edu.

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. [Cancer Res 2007;67(10):4630–7]

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