Date of Award
Master of Science in Biomedical Sciences
Dianzheng Zhang, PhD
Ruth Borghaei, PhD
Heather Montie, PhD
Prostate cancer is one of the biggest threats to men’s health in the western world and it accounts for the second largest number of male cancer-related deaths in the United States. It is well established that prostate cancer cells depend on the androgen/androgen receptor pathway. Therefore, androgen deprivation therapy (ADT) has become the primary treatment option for prostate cancer. Patients with metastatic prostate cancer who receive (ADT) have shown increased quality of life. However, survival benefit with ADT is reduced dramatically in castration-resistant prostate cancer (CRPC). Androgen receptor (AR) continues to be functional in CRPC through various mechanisms. It is becoming evident that AR-V7, an AR variant with constitutive transcriptional activity, plays crucial roles in the development of CRPC. In order to study the mechanism of AR-V7’s actions and the ability of resveratrol to repress AR-V7, we ectopically expressed AR-V7 in PC3 cells and treated the cells with different concentrations of resveratrol. Resveratrol represses AR-V7 transcriptional activity in a dose-dependent manner evidenced by levels of the AR target gene PSA. Mechanistically, we found that under our specific experimental conditions resveratrol down-regulates AR-V7 protein levels post-transcriptionally without affecting AR-V7 subcellular location. Given the fact that resveratrol potentially represses endogenous AR-V7 transcriptional activity at the transcriptional level, resveratrol could become an option in CPRC treatment.
Wilson, Sarah R., "Developing a Model System to Study the Mechanisms of Resveratrol Inhibition of AR-V7 Transcriptional Activity" (2016). PCOM Biomedical Studies Student Scholarship. 160.