Accession Number:

ADA503788

Title:

Role of X-linked Inhibitor of Apoptosis in Breast Cancer

Descriptive Note:

Final rept. 15 Mar 2006-14 Mar 2009

Corporate Author:

MICHIGAN UNIV ANN ARBOR

Personal Author(s):

Report Date:

2009-04-01

Pagination or Media Count:

32.0

Abstract:

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.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE