Regulation of TRADD by Androgens in Prostate Cancer

Diping Wang

Androgen treatment in prostate cancer cells

Androgens have been suggested to protect prostate cells from death-receptor induced apoptosis. We found that androgen treatment up-regulates the expression of TRADD in prostate cancer cells and hypothesized that androgens inhibit death receptor induced apoptosis through the induction of TRADD and activiation of NF-kappaB.

Track: BMB / Tumor Biology; Thesis Advisor: Donald J. Tindall

Prostate cancer is the most common malignancy and the second leading cause of cancer death in American men. Currently, androgen ablation is the primary treatment for advance prostate cancer. However, inevitably, these tumors will progress to an androgen-depletion independent (ADI) state. Prostate cancers at this stage are unresponsive to androgen ablation treatment. Our lab is focusing on exploring the molecular mechanisms by which prostate cancer cells progress to the ADI state.

Besides the alteration of sensitivity to androgen ablation treatment, progression of prostate cancer often is associated with defects in apoptotic signaling pathways. It has been suggested that the treatment of death receptor ligands, like TNF-_ and TRAIL, is still a very effective strategy in some cancers, while other cancers are resistant to this treatment. Accumulating evidences suggest that androgens can modulate the death receptor induced signaling pathway and modify the effects of the treatment of TNF-_ or TRAIL. To develop a more efficient therapeutic strategy, it is very important to understand the cross-talk between these two signaling pathways. My project is focusing on the modulation of TNF-_ induced signals by androgens. We observed that androgen treatment modulates the expression of the TNFR1-associated death domain protein (TRADD), a death receptor adaptor protein in the TNF-_ signaling pathway. We hypothesize that androgens can modulate the TNF-_ signaling pathway and protect cells from apoptosis through the regulation of TRADD. My current goal is to identify the underlying mechanisms of this regulation and to test this hypothesis.