Tillman J Erin, Yuan Jialing, Gu Guangyu, Fazli Ladan, Ghosh Ritwik, Flynt Alex S, Gleave Martin, Rennie Paul S, Kasper Susan
Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232-2765, USA.
Cancer Res. 2007 May 15;67(10):4630-7. doi: 10.1158/0008-5472.CAN-06-4556.
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.
癌基因DJ-1与多种癌症相关，包括前列腺癌，在前列腺癌中它可被雄激素和抗雄激素稳定。然而，关于DJ-1在前列腺癌中的表达模式和功能的数据很少。为了研究DJ-1在前列腺中的功能，进行了酵母双杂交筛选以鉴定新的DJ-1结合蛋白。雄激素受体（AR）被鉴定并确认为DJ-1的结合伙伴。这是DJ-1直接与AR相互作用的首个证据。我们还表明，DJ-1表达的调节可调控AR的转录活性。重要的是，DJ-1的亚细胞定位以及与AR的相互作用均受雄激素和抗雄激素的调控。此外，对两个人类前列腺癌组织芯片进行了免疫组织化学染色，提供了DJ-1在前列腺中的首个大规模表达分析。DJ-1的表达不随 Gleason分级改变，但在雄激素剥夺治疗后增加，表明它可能参与雄激素非依赖性的发展。这些数据提供了一种新机制，即DJ-1介导的AR调节可能促进前列腺癌向雄激素非依赖性进展。
