Prostate Cancer--Mechanisms of Bax induced Cell Death

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the development of androgen-independence by prostate cancer cells is a major hurdle in the treatment of prostate cancer with conventional therapies. The major molecular defect is that the cancer cells fail to initiate programmed cell death (apoptosis) in response to various eupeptic stimuli. Recently we have found that over expression of bad, which is a pro-apoptotic molecule and a counterpart of BCL-2, includes apoptose in prostate cancer cells. In fact, androgen-independent LNCaP cells are even more sensitive to Bad-induced cell death than their androgen-dependent counterparts. Furthermore, subcellular localizations of Bad appear to be different in androgen-dependent and independent LNCaP cells. We hypothesize that Bad may play a critical role in the balance between cell survival and death in androgen-independent prostate cancers. We propose to investigate the molecular mechanisms underlying Bad-induced apoptosis in prostate cancer cells, as well as its relationship to the androgen-independent in vitro and in vivo. This work is novel as it will shed light on the interplay between an eupeptic pathway and androgen regulation and might have therapeutic implications for prostate cancer. The training environment for the applicant is excellent. Dr. Shustung Liam, the ,mentor, has been studying androgen regulation and prostate cancer for more tan 40 years and his group has made several ground breaking contributions to the field. The Ben May Institution for Cancer Research has long tradition for prostate cancer research, starting from the Noble Prize winning work of Dr. Huggins on treatment of prostate cancer. The University of Chicago has several excellent prostate cancer research programs. With many investigators and exports working in the field of prostate cancer and many Core facilities, including a prostate tissue bank. With the excellent training I have received in the fields of cycle regulation, apoptosis and gene therapy, I am confident that I will be able to pursue the proposed studies and make a successful transition into the front tier of prostate cancer research. The financial support provided by this NIH award will allow me to complete my training and to launch my carrier ad an independent investigator in an academic setting.