Date of Award

8-2016

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Dianzheng Zhang, PhD

Second Advisor

Ruth Borghaei, PhD

Third Advisor

Heather Montie, PhD

Abstract

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.

Included in

Oncology Commons

COinS