repressive effects of resveratrol on androgen receptor transcriptional activity压抑的白藜芦醇对雄激素受体转录活性的影响.pdfVIP

Repressive Effects of Resveratrol on Androgen Receptor Transcriptional Activity 1. 2. 2 2 3 1 Wen-feng Shi , Melanie Leong , Ellen Cho , Joseph Farrell , Han-chun Chen , Jun Tian , Dianzheng Zhang2,3* 1 Department of Blood Purification, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China, 2 Department of Biochemistry and Molecular Biology and Center for Chronic Disorders of Aging, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania, United States of America, 3 Department of Biochemistry, School of Biological Science and Technology, Central South University, Changsha, Hunan, People’s Republic of China Abstract Background: The chemopreventive effects of resveratrol (RSV) on prostate cancer have been well established; the androgen receptor (AR) plays pivotal roles in prostatic tumorigenesis. However, the exact underlying molecular mechanisms about the effects of RSV on AR have not been fully elucidated. A model system is needed to determine whether and how RSV represses AR transcriptional activity. Methodology: The AR cDNA was first cloned into the retroviral vector pOZ-N and then integrated into the genome of AR- negative HeLa cells to generate the AR(+) cells. The constitutively expressed AR was characterized by monitoring hormone- stimulated nuclear translocation, DNA binding, and transcriptional activation, with the AR(-) cells serving as controls. AR(+) cells were treated with RSV, and both AR protein levels and AR transcriptional activity were measured simultaneously. Chromatin immunoprecipitation (ChIP) assays were used to detect the effects of RSV on the recruitment of AR to its cognate element (ARE). Results: AR in the AR (+) stable cell