The Role of the IAP Gene Family in Breast Cancer.
Annual rept. 1 Jul 97-30 Jun 98
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 result in an increased resistance of tumors to apoptosis and thereby render them resistant to many chemotherapeutic drugs. The inhibitor of apoptosis proteins IAP are a family of anti-apoptotic proteins that are conserved across species. This family of proteins includes four human c-IAP1HIAP2c-IAP2HIAP1XIAPhILPsurvivin, two Drosophilia DIAP1DIAP2, two yeast SpBIR1ScBIR2 and two C. Elegans homologs. I have shown that the IAPS are direct inhibitors of specific members of the cysteine family of proteases, caspases-3,-6,-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 shown that IAPs can suppress different apoptotic pathways induced by various stimuli, by inhibiting distinct caspase members. These observations may contribute to the development of novel pharmacological agents that modulate these components to improve tumor response in carcinomas.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research