Impairment of Fas-antigen expression in adriamycin-resistant but not TNF-resistant MCF7 tumor cells

International Journal of Cancer. Journal International Du Cancer
Z CaiS Chouaib

Abstract

Anti-cancer drugs and cytotoxic cytokines such as members of the TNF/Fas-ligand family play a predominant role in apoptosis induction in tumor cells, and are critical in cancer therapy. In this study we used the human breast-carcinoma cell line MCF7, its derivatives MCF7Adr (resistant to adriamycin) and R-A1 (resistant to TNF), to determine the impact of acquired drug and cytokine resistance on susceptibility to Fas-induced cytotoxicity and Fas-antigen expression. While MCF7 and R-A1 cells were killed by anti-Fas in the presence of IFN-gamma, MCF7Adr was found to be resistant to Fas-mediated apoptosis. This resistance was correlated with a loss of surface Fas-protein expression. Fas-gene transfer in MCF7Adr resulted in high sensitivity to Fas-mediated cytotoxicity, indicating that the Fas signalling pathway is virtually intact in this cell line. Over-expression of the MDR1 gene in MCF7 following gene transfer did not affect Fas expression and anti-Fas sensitivity, suggesting that the P-gp-mediated multidrug-resistance phenotype is not directly involved in the loss of Fas expression, contrary to what has been observed by others in T-cell lines. Furthermore, the down-regulation of Fas expression and subsequent resistance to anti-...Continue Reading

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Citations

Jan 15, 2003·Proceedings of the National Academy of Sciences of the United States of America·Christel MassonJaime F Angulo
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Oct 1, 2010·Breast Cancer Research and Treatment·Chao ShenSongbin Fu
Mar 21, 2006·Journal of Immune Based Therapies and Vaccines·M Karen NewellRobert E Camley

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