XIAP as a Molecular Target for Therapeutic Intervention in Prostate Cancer
Final rept. 23 Sep 2004-22 Sep 2007
MICHIGAN UNIV REGENTS ANN ARBOR DIV OF RESEARCH DEVELOPMENT AND ADMINISTRATION
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This is the final report of our CDMRP-funded research grant. Our study comprised of two research aims to validate and examine the therapeutic potential of targeting XIAP for the treatment of prostate cancer. In the first of the two Aims, we generated cell lines in which XIAP was suppressed, using lentiviral-based RNA interference delivery system. Additionally, we reconstituted these lines with a panel of XIAP variants lacking either the caspase inhibitory or the E3 ubiquitin ligase properties of this molecule. In functional studies, we have obtained important. We have made very significant progress towards the completion of the goals proposed in this award. In the first of the two Aims, we experimental data concerning the relative contribution of these different aspects of XIAP to the cytoprotective effects of this protein, although for technical reasons the use of these lines in xenograft studies generated excessive variation. In the second Aim, we have examined XIAP expression in the TRAMP transgenic murine model of prostate cancer. These studies have revealed an interesting trend towards Xiap-deficient animals being more susceptible to tumors, which correlates with some recent clinical data on XIAP expression in prosate cancer patients. Thus, these data have significant implications for the clinical use of XIAP antagonists as anti-cancer agents. Finally, the data described above are included in three manuscripts are currently in review.
- Anatomy and Physiology
- Medicine and Medical Research