Induced Expression of Androgen Receptor in Androgen Independent Prostate Cancer Cells Using an I kappa B alpha "Super Repressor"
Abstract
Advanced prostate cancer continues to kill 32,000 men per year in the United States. Despite strides in obtaining partial, temporary remissions in men with advanced disease through the use of hormones and chemotherapeutic agents, there is no curative therapy for advanced prostate cancer. Most prostate cancers are responsive to androgens, and androgen withdrawal (i.e., surgical or medical castration) is the main form of treatment for advanced (i.e. disseminated) disease.1 The failure of primary hormone therapy is attributed to androgen-independent tumor expansion. Although the androgen receptor (AR) is present in these cells, it is nonfunctional.2 These cells have been shown to grow by other means. Many androgen independent cells survive by acquired resistance to many cell death inducing factors. At this point, there is no clear explanation as to why prostate cancer cells develop androgen independence. We believe that a molecule called CBP CREB (cAMP response element binding protein)-binding protein may play a critical role. CBP associates with several other sequence-specific factors, including NF-kappa B and AR. Both NF-kappa B and AR require CBP for their activation. We investigated the effects of inhibitors of NF-kappa B as well as other chemotherapeutic agents to treat hormone refractory prostate cancer. -I
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADA410579
Entities
People
- Carlton R. Cooper
- Kenneth J. Pienta
Organizations
- University of Michigan