Cancer Research Infection and Cancer: Biology, Therapeutics, and Prevention  AACR Conference on Molecular Diagnostics - 2008
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[Cancer Research 60, 5673-5680, October 15, 2000]
© 2000 American Association for Cancer Research


Biochemistry and Biophysics

Interferon-{gamma} Treatment Elevates Caspase-8 Expression and Sensitizes Human Breast Tumor Cells to a Death Receptor-induced Mitochondria-operated Apoptotic Program1

Carmen Ruiz-Ruiz, Cristina Muñoz-Pinedo and Abelardo López-Rivas2

Instituto de Parasitología y Biomedicina Consejo Superior de Investigaciones Centificas, 18001 Granada, Spain

In this report, we have assessed the role of IFN-{gamma} as a sensitizing agent in apoptosis mediated by activation of death receptor CD95 in breast tumor cells. Treatment of the tumor cell lines MCF-7 and MDA-MB231 with IFN-{gamma} significantly facilitated apoptosis induced by CD95 receptor ligation at the plasma membrane, independently of p53 status. In contrast, IFN-{gamma} treatment did not enhance the apoptotic effect of the DNA-damaging drug, doxorubicin. Analysis of apoptosis regulators indicated that caspase-8 mRNA and protein levels were up-regulated in both of the cell lines after treatment with IFN-{gamma}. Furthermore, IFN-{gamma} sensitized MCF-7 and MDA-MB231 cells to CD95-mediated activation of caspase-8, induction of cytochrome c release from mitochondria, and processing of caspase-9. Release of cytochrome c, caspases activation, and apoptosis were prevented in MCF-7 cells overexpressing Bcl-2. Altogether these results indicate that IFN-{gamma}, maybe through the elevation of caspase-8 levels, sensitizes human breast tumor cells to a death receptor-mediated, mitochondria-operated pathway of apoptosis.




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