Survival Signaling in Prostate Cancer: Role of Androgen Receptor and Integrins in Regulating Survival
Abstract
Although prostate cancer patients initially respond to androgen ablation therapy, they ultimately relapse and the tumor no longer responds to androgen, offering little hope for long-term disease-free survival. However, inhibition of AR expression in cells leads to cell death. This suggests that prostate cancer cells are still dependent on AR for survival, even if the cells are no longer responding to physiological levels of androgen. We have demonstrated that expression of AR in PC3 prostate tumor cells can rescue cells from death induced by inhibition of PI-3K. AR expression leads to increased expression of alpha6Beta1-integrin and subsequent increased expression of the pro-survival protein Bcl-xL. Blocking either leads to cell death. We have also generated an in vitro differentiation model of the prostate epithelium which generates differentiated AR-expressing secretory cells that recapitulate many in vivo characteristics. Using this model, we have demonstrated that prostate secretory cells are dependent on PI-3K and E-cadherin, but not EGFR, integrins, or androgen, signaling for cell survival.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2009
- Accession Number
- ADA501749
Entities
People
- Laura Lamb