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

Int J Cancer. 1996 Nov 15;68(4):535-46. doi: 10.1002/(SICI)1097-0215(19961115)68:4<535::AID-IJC21>3.0.CO;2-2.


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-Fas were observed in drug-resistant human ovarian-carcinoma IGR-OV1/VCR cells and leukemic lymphoblast CEM/VLB cells, suggesting that the alteration of Fas expression following drug-resistance selection is not restricted to one cell type.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Antibiotics, Antineoplastic / pharmacology*
  • Doxorubicin / pharmacology*
  • Drug Resistance
  • Gene Expression Regulation, Neoplastic*
  • Gene Transfer Techniques
  • Humans
  • Interferon-gamma / pharmacology
  • RNA, Messenger / analysis
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Vinblastine / pharmacology
  • Vincristine / pharmacology
  • fas Receptor / genetics*
  • fas Receptor / physiology


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibiotics, Antineoplastic
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • Vincristine
  • Vinblastine
  • Doxorubicin
  • Interferon-gamma