| UV-induced apoptosis is mediated independent of caspase-9 in MCF-7 cells: a model for cytochrome c resistance. | |
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MedLine Citation:
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PMID: 12954616 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 down-stream 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. |
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Authors:
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Heather A Ferguson; Peter M Marietta; Carla L Van Den Berg |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. Date: 2003-09-03 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 278 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2003 Nov |
Date Detail:
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Created Date: 2003-11-10 Completed Date: 2003-12-24 Revised Date: 2008-05-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 45793-800 Citation Subset: IM |
Affiliation:
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School of Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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metabolism Apoptosis* Blotting, Western Breast Neoplasms / metabolism Caspase 3 Caspase 7 Caspase 9 Caspases / metabolism, physiology* Cell Line Cell Line, Tumor Cell Survival Cytochromes c / metabolism* Enzyme Activation Humans Insulin-Like Growth Factor I / metabolism Microscopy, Fluorescence Poly(ADP-ribose) Polymerases / metabolism Precipitin Tests Proteins / metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism RNA / metabolism Time Factors Transfection Ultraviolet Rays X-Linked Inhibitor of Apoptosis Protein |
| Grant Support | |
ID/Acronym/Agency:
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CA89288A/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/X-Linked Inhibitor of Apoptosis Protein; 0/XIAP protein, human; 63231-63-0/RNA; 67763-96-6/Insulin-Like Growth Factor I; 9007-43-6/Cytochromes c; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/CASP7 protein, human; EC 3.4.22.-/CASP9 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 7; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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