Role of Androgen Receptor in Growth of Androgen Independent Prostate Cancer
Abstract
Hormone therapy is an effective treatment for advanced hormone sensitive (HS) prostate cancer. However, the treatment is short-lived and hormone refractory (HR) cancer eventually develops. Through gene profiling using seven pairs of HS and HR xenografts, we identified overexpression of androgen receptor (AR) is the only consistent change in the progression of prostate cancer. In the first grand period (01/02-10/03), we confirmed that AR protein is elevated in HR tumors. Using lentivirus and retrovirus systems, we were able to overexpress AR in HS prostate cancer cells. In vitro and in vivo experiments demonstrated that overexpression of AR is sufficient for HS-to-HR transition. We also developed a system (shRNA) to knockdown AR in HR LNCaP cells and shown that AR-knockdown abolished HR phenotype in vitro. In the last grand period (01/03-01/04), we demonstrated that overexpression of AR is required for hormone refractory prostate cancer in vivo using both LAPC4 and LNCaP cells. Although, we were unable to obtain conclusive results to determine the mechanisms for AR overexpression, we demonstrated that gene amplification is not the sole cause of the overexpression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2004
- Accession Number
- ADA422345
Entities
People
- Charlie D. Chen
Organizations
- University of California, Los Angeles