Induced Expression of Androgen Receptor in Androgen Independent Prostate Cancer Cells Using an IkBalpha Super Repressor

摘要

Advanced prostate cancer continues to kill 29,000 men annually in the United States. Despite strides in obtaining extended remissions through the use of hormones and chemotherapeutic agents, there is still no curative therapy for this devastating disease. While most prostate cancers are responsive to androgens and while androgen withdrawal is the main form of treatment, the failure of primary hormone therapy is attributed to androgen-independent tumor expansion. Mechanisms for the transition from androgen-sensitive to androgen- refractory disease are currently not well understood. We proposed to investigate the role of TNF-alpha-mediated NF-icB signaling in androgen-sensitive and - insensitive prostate cancer, as many androgen-independent prostate cancer cell lines exhibit resistance to this pathway and as TNF-alpha is detected at high serum levels in relapsing prostate cancer patients compared to those in remission or untreated. We subsequently demonstrated activation of TNF-alpha- induced apoptosis with an IkB-alpha super repressor and relieved NF-KB repression of the androgen receptor in androgen-independent prostate cancer cell lines cells. During this current funding period we report generation of a non- invasive quantitative murine model for metastatic prostate cancer. Thus, we now are poised to evaluate these novel insights of androgen interactions in vivo, a critical step toward designing novel therapeutic strategies.