Yeh S, Chang C
Department of Medicine and University of Wisconsin Comprehensive Cancer Center, University of Wisconsin, Madison 53792, USA.
Proc Natl Acad Sci U S A. 1996 May 28;93(11):5517-21. doi: 10.1073/pnas.93.11.5517.
The androgen receptor (AR) is a member of the steroid receptor superfamily that plays an important role in male sexual differentiation and prostate cell proliferation. Mutations or abnormal expression of AR in prostate cancer can play a key role in the process that changes prostate cancer from androgen-dependent to an androgen-independent stage. Using a yeast two-hybrid system, we were able to isolate a ligand-dependent AR-associated protein (ARA70), which functions as an activator to enhance AR transcriptional activity 10-fold in the presence of 10(-10) M dihydrotestosterone or 10(-9) M testosterone, but not 10(-6) M hydroxyflutamide in human prostate cancer DU145 cells. Our data further indicated that ARA70 Will only slightly induce the transcriptional activity of other steroid receptors such as estrogen receptor, glucocorticoid receptor, and progesterone receptor in DU145 cells. Together, these data suggest that AR may need a specific coactivator(s) such as ARA70 for optimal androgen activity.
雄激素受体（AR）是类固醇受体超家族的成员，在男性性别分化和前列腺细胞增殖中起重要作用。前列腺癌中AR的突变或异常表达在前列腺癌从雄激素依赖阶段转变为雄激素非依赖阶段的过程中起关键作用。利用酵母双杂交系统，我们能够分离出一种配体依赖性AR相关蛋白（ARA70），在人前列腺癌DU145细胞中，当存在10^(-10) M双氢睾酮或10^(-9) M睾酮时，该蛋白作为激活剂可将AR转录活性提高10倍，但在存在10^(-6) M羟基氟他胺时则不然。我们的数据进一步表明，ARA70在DU145细胞中只会轻微诱导其他类固醇受体如雌激素受体、糖皮质激素受体和孕激素受体的转录活性。总之，这些数据表明AR可能需要特定的共激活因子如ARA70来实现最佳雄激素活性。
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