Accession Number:

ADA422345

Title:

Role of Androgen Receptor in Growth of Androgen Independent Prostate Cancer

Descriptive Note:

Annual summary rept. 15 Dec 2001-14 Dec 2003

Corporate Author:

CALIFORNIA UNIV LOS ANGELES

Personal Author(s):

Report Date:

2004-01-01

Pagination or Media Count:

6.0

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 0102-1003, 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 0103-0104, 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.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE