Role of Hsp90 in Androgen-Refractory Prostate Cancer

A major challenge in prostate cancer research is to develop novel therapies that can delay or prevent the progression of androgen-sensitive prostate cancer to androgen-independence. Androgen receptor AR is often overexpressed and plays an essential role in androgen-refractory prostate tumors. Our preliminary studies suggest that heat shock protein 90 Hsp90 is required for androgen-independent AR nuclear localization in androgen-refractory prostate cancer cells. This project will test our research hypothesis that Hsp90 plays a critical role in ligand-independent AR nuclear localization, an essential step leading to androgen-refractory prostate cancer. In the last year of the funding period, we have constructed lenti-viral vectors for expressing siRNA specific for Hsp90. Experiments are on the way to test if downregulation of Hsp90 protein will cause alterations in AR intracellular localization and function in prostate cancer cells.