Androgen Receptor-Mediated Escape Mechanisms From Androgen Ablation Therapy
Abstract
Too many prostate-cancer treatments, especially those relying on the suppression of androgen, eventually fail to slow the advance of the disease. One explanation for this situation is the absence of any systematic knowledge on the role and function of the androgen receptor (AR) in the course of prostate cancer development. Recent findings indicate that the AR is the key master regulator (transcription factor) that determines disease progression to androgen independence, which ultimately contributes to death from prostate cancer. During the third year of this grant funding, we concentrated our efforts on the understanding of how transcriptional control of the AR at target loci is achieved as the PCa cells escape from androgen ablation therapy to become treatment resistant. We found that histone H3 lysine 4 methylation patterns are unique in ablation resistant PCa cells. Furthermore, globally the AR and certain histone modifications co-locate in discreet areas in the nucleus. In the final no-cost extension year of the grant we will complete our work on other AR traget genes. Thus, armed with a deeper knowledge of the hormonal and receptor requirements as well as mechanisms associated with prostate cancer growth and expansion, we may be able to develop therapies that prolong lives. Understanding the behavior of the AR, as documented above, is a first step in that quest.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2007
- Accession Number
- ADA476751
Entities
People
- Gerhard A. Coetzee
- Jia Li
- Judd Rice
Organizations
- University of Southern California