Research Abstracts Online
2008 - March 2009
University of Minnesota Twin Cities
Academic Health Center
Masonic Cancer Center
PI: Scott M. Dehm
The Role of the Androgen Receptor in Prostate Cancer Progression
In the event that surgery or radiation do not cure prostate cancer (PCa), locally recurrent or metastatic disease can be treated via systemic blockade of the production or action of androgens. This so-called androgen ablation therapy specifically inhibits the androgen receptor (AR), a steroid hormone transcription factor. The major limitation is that androgen ablation is not curative, and PCa will invariably progress to an aggressive and lethal androgen-refractory or androgen depletion-independent (ADI) phenotype. An important concept that has been established is that ADI PCa remains an AR-dependent disease. As such, there is consensus that new modes of AR inhibition could be used to successfully treat ADI PCa. This researcher has identified a novel region of the AR N-terminal domain (NTD) that mediates transcriptional activation exclusively under conditions of no/low androgens. This NTD transcriptional activation domain was mapped to a discrete WHTLF motif, and shown to function as a bona fide transcriptional activator in isolation. The goal of this project, which uses the CGL, is to investigate the role of the AR WHTLF motif in prostate cancer progression.