Date of Award

Spring 2004

Document Type

Restricted Thesis

Terms of Use

© 2004 Stephen L. Cook. All rights reserved. Access to this work is restricted to users within the Swarthmore College network and may only be used for non-commercial, educational, and research purposes. Sharing with users outside of the Swarthmore College network is expressly prohibited. For all other uses, including reproduction and distribution, please contact the copyright holder.

Degree Name

Bachelor of Arts

Department

Biology Department

First Advisor

Elizabeth Ann Vallen

Abstract

Prostate cancers display a unique dependence upon androgens for both growth and survival. Unfortunately, treatments intended to eliminate androgens are only temporarily effective, as pathways regulating the activity of the androgen receptor (AR) are eventually circumvented. Hence, current prostate cancer research aims to understand the mechanisms by which AR activity is controlled. It has been previously shown that cyclin D1 is a potent inhibitor of AR function; however, the role of cyclin D1 in prostate cancer progression and initiation remains elusive. We show that cyclin Dl inhibits AR transactivation of multiple androgen responsive elements including: mouse mammary tumor virus (MMTV) and probasin. The activity of the AR phosphorylation mutant S650A was also repressed by cyclin D1. In addition, we examine AR mobility in vivo using fluorescence recovery after photobleaching (FRAP) and a GFP-AR fusion protein. We show herein that FRAP can effectively measure the AR-GFP movement, demonstrating that the receptor is less mobile in the presence of ligand. Additionally,AR mobility is affected by the chromatin state of target genes, which cyclin D1 is hypothesized to modify. These data suggest cyclin D1 to be a general inhibitor of AR and begin to explain the mechanism by which cyclin Dl affects AR function.

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