DJ-1 binds androgen receptor directly and mediates its activity in hormonally treated prostate cancer cells
DJ-1 binds androgen receptor directly and mediates its activity in hormonally treated prostate cancer cells
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DOI：
10.1158/0008-5472.can-06-4556
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发表时间：
2007-05-15
期刊：
影响因子：
11.2
通讯作者：
Kasper, Susan
中科院分区：
文献类型：
--
作者：
Tillman, J. Erin;Yuan, Jialing;Kasper, Susan
致癌基因DJ-1与多种癌症有关，包括前列腺癌，其中它可以通过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。为了阐明DJ-1在前列腺中的功能，进行酵母双杂交筛选以鉴定新型DJ-1结合蛋白。雄激素受体（AR）被鉴定并确认为DJ-1结合伴侣。这是DJ-1直接与AR相互作用的第一个证据。我们还表明，DJ-1的表达调节AR转录活性的调制。重要的是，DJ-1的亚细胞定位和与AR的相互作用都受到雄激素和抗雄激素的调节。此外，在两个人前列腺癌组织阵列上进行免疫组织化学染色，提供了前列腺中DJ-1的首次大规模表达分析。DJ-1的表达不随Gleason模式而改变，但在雄激素剥夺治疗后增加，表明其可能参与雄激素非依赖性的发展。这些数据提供了一种新的机制，其中DJ-1介导的AR调节可能促进前列腺癌进展为雄激素非依赖性。
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.