Caveolin-1 Modulates Androgen Receptor Signaling in Advanced Prostate Cancer
Abstract
The underlying machanism of the progression of prostate cancer to hormone-independent disease is poorly understood. Neoexpression of caveolin-l, a scaffold protein associated with caveolae membrane microdomains, has been shown to correlate with hormone resistance and metastasis in both human and mouse prostate cancer models. We found overexpressing caveolin-l in human prostate cancer cells positively regulate androgen receptor transactivation activity. We identify in cellular models that modulating caveolin expressing levels dramatically alter the sensitivity of AR to androgen stimulation. We hypothesize that caveolin-l sacffoding signal complex play a regulatory role in AR activation pathway. The immediate goal of the present proposal aims to identify and characterize the sub-moleclar domains involved in AR/caveolin interaction. In current funding year, we demonstrated a cross-talk between the caveolin-1-associated signal pathway and AR-mediated transcriptional activity in our first funding year. Several lines of evidence, biological as well as biochemical, support the notion of an androgen-dependent physiological interaction between these two pathways. Overall, our results suggest that caveolin-l plays a role as a convergent point for AR cross-talk with other cellular signal transduction pathways. These findings pave the way to further define the underlying signal cross-talk in AR-mediated transactivation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2003
- Accession Number
- ADA414469
Entities
People
- Michael L. Lu
Organizations
- Brigham and Women's Hospital