Androgen Receptor-Mediated Escape Mechanisms from Androgen Ablation Therapy
Abstract
Too many prostrate-cancer treatments, especially those relying on the suppression ofandrogen, 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 prostrate cancer development. Recent findings indicate that the AR is the key master regulator that determines disease progression to androgen independence, which ultimately contributes to death from prostate cancer. During the first year of this grant funding, we concentrated our efforts on the understanding of ligand-independent AR signaling in cells which are resistant to ablation manipulations. Thus, we defined the role of protein kinase A pathway CREB as a ligand-independent mechanism in AR- mediated transcription at the prostate-specific antigen locus. We also found that certain coactivators mediate the interaction between the amino- and carboxyl-termini of the androgen receptor Unexpectedly, however, in our latest work we demonstrated that although androgen ablation resistant cells are dependent on AR signaling for PSA expression, the AR was not recruited to the PSA enhancer or promoter sites where it normally mediates PSA expression. This result was published this month in Cancer Research. We are in the process of unraveling the mechanism of this interesting finding. Armed with a deeper knowledge of the hormonal and receptor requirements as well as mechanisms associated with prostrate cancer growth and expansion, we can develop therapies that prolong lives. Understanding the behavior of the androgen receptor is a first step in that quest.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2005
- Accession Number
- ADA446298
Entities
People
- Gerherd A. Coetzee
- Jia Li
- Judd Rice
Organizations
- California State University, Los Angeles