التفاصيل البيبلوغرافية
| العنوان: |
UV-induced Apoptosis Is Mediated Independent of Caspase-9 in MCF-7 Cells. |
| المؤلفون: |
Ferguson, Heather A.1, Marietta, Peter M.1, Van Den Berg, Carla L.1 carla.vandenberg@UCHSC.edu |
| المصدر: |
Journal of Biological Chemistry. 11/14/2003, Vol. 278 Issue 46, p45793-45800. 8p. 7 Diagrams, 1 Graph. |
| مصطلحات موضوعية: |
*APOPTOSIS, *ULTRAVIOLET radiation, *MITOCHONDRIA |
| مستخلص: |
The importance of the mitochondria in UV-induced apoptosis has become increasingly apparent. Following DNA damage cytochrome c and other pro-apoptotic factors are released from the mitochondria, allowing for formation of the apoptosome and subsequent cleavage and activation of caspase-9. Active caspase-9 then activates downstream caspases-3 and/or -7, which in turn cleave poly(ADP)-ribose polymerase (PARP) and other downstream targets, resulting in apoptosis. In an effort to understand the mechanisms of Akt-mediated cell survival in breast cancer, we studied the effects of insulin-like growth factor (IGF)-I treatment on UV-treated MCF-7 human breast cancer cells. Apoptosis was induced in MCF-7 cells after UV treatment, as measured by caspase-7 and PARP cleavage, and IGF-I co-treatment protected against this response. Surprisingly caspase-9 cleavage was unchanged with UV and/or IGF-I treatment. Using MCF-7 cells overexpressing caspase-3 we have shown that resistance of caspase-9 to cleavage was not altered by the expression of caspase-3. Furthermore, overexpression of caspase-9 did not enhance PARP or caspase-7 cleavage after UV treatment. Because caspase-8 was activated with UV treatment alone, we believe that UV-induced apoptosis in MCF-7 cells occurs independently of cytochrome c and caspase-9, supporting the existence of a cytoplasmic inhibitor of cytochrome c in MCF-7 cells. We anticipate that such inhibitors may be overexpressed in cancer cells, allowing for treatment resistance. [ABSTRACT FROM AUTHOR] |
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