Date of Submission

Spring 2012

Academic Program

Biology

Project Advisor 1

Philip Johns

Project Advisor 2

John Ferguson

Abstract/Artist's Statement

Prostate cancer is the second leading cause of cancer-related death among men in the United States. Primary tumors require androgen stimulation to survive and proliferate; however, as the cancer progresses, these cells lose androgen sensitivity and undergo an epithelial-to-mesenchymal transition (EMT). This transition is associated with a loss of microRNA-200c (miR-200c) expression, enhanced epidermal growth factor receptor (EGFR) expression, and ultimately increased ability to metastasize. Previous studies show that re-expression of miR-200c is sufficient for a reversal of EMT: mesenchymal-to-epithelial transition (MET). However, the effects of miR-200c on androgen sensitivity and EGFR signaling in MET remain undefined. In this study I hypothesize that re-expression of miR-200c reduces prostate cancer aggressiveness by reintroducing androgen-regulated growth and modifying EGFR signaling. Using quantitative PCR, I examined the effects of androgen and EGF treatments on expression of androgen receptor (AR), EGFR, and miR-200c in several cell lines, including ones that over-express miR-200c (PC3-200c) and weakly express miR-200c (PC3 and PC3-SRM). Following androgen treatment PC3-200c cells showed a marked increase in miR-200c expression and a simultaneous decrease in EGFR expression. Meanwhile, there were no significant changes in EGFR expression for PC3 and PC3-SRM, no change in miR-200c expression for PC3, and a relatively small decrease in miR-200c expression for PC3-SRM cells. Taken together, the proliferation and gene expression results suggest that over-expression of miR-200c reverses metastatic behavior in prostate cancer cells by reinstating androgen regulation of growth and reducing aggressiveness in EGFR signaling. These findings have important clinical implications, as androgen inhibitors are common treatments for early stage androgen-sensitive prostate cancer tumors, but metastatic tumors remain largely untreatable. This research on miR-200c antitumor activity may provide insights into the use of existing therapies for typically incurable tumors.

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