Role of X-linked Inhibitor of Apoptosis in Breast Cancer
Final rept. 15 Mar 2006-14 Mar 2009
MICHIGAN UNIV ANN ARBOR
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XIAP has been identified as a potential target for breast cancer therapeutics, but the specific functions of XIAP that contribute to breast cancer development or progression remain unknown. The major tasks for this phase of this project involved evaluating breast cancer cell lines depleted in XIAP expression in tumor growth models in vivo and anchorage-independent growth models in vitro. Surprisingly, XIAP did not affect cancer cell growth in these models, and cell lines with rescued expression of XIAP did not demonstrate increased tumorigenesis compared to XIAP-deficient cells. These cell lines have been evaluated for sensitivity to apoptotic stimuli, and XIAP was a necessary anti-apoptotic molecule in these cells and required caspase-inhibitory residues D148 and W310 for this activity. This knowledge will be valuable to guide the development of therapeutics that target XIAP, which are currently in phase III clinical trials.
- Medicine and Medical Research