The Role of the IAP Gene Family in Breast Cancer
Annual rept. 1 Jul 1998-30 Jun 1999
BURNHAM INST LA JOLLA CA
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Dysregulation of the control of both cellular proliferation and cell death contributes to tumor growth. Consistent with this hypothesis, overexpression of genes that block apoptosis is observed in tumors. Furthermore, upregulation of genes that confer survival results in an increased resistance of tumors to apoptosis and thereby renders them resistant to many chemotherapeutic drugs. The inhibitor of apoptosis proteins IAps are a family of anti-apoptotic proteins that are conserved across species. This family of proteins includes six human members, including c-TAPlHIAP2, c-TAP2HTAPl, xIAPHILP, survivin, NAIP, and BRUCE. We have shown that the IAPs are direct inhibitors of specific members of the cysteine family of cell death proteases, caspases-3, -7, and -9. The caspases play a central role as effectors in the apoptotic cascade and their inhibition contributes to tumor growth and resistance to chemotherapeutic agents. We have found that IAPs are over-produced in some types of cancer, including adenocarcinomas and the breast. These observations lay the foundation for eventually abrogating the effects of IAPs and restoring apoptosis sensitivity to cancers.
- Medicine and Medical Research