IFN-gamma induces cell growth inhibition by Fas-mediated apoptosis: requirement of STAT1 protein for up-regulation of Fas and FasL expression.
The mechanism by which IFN-gamma inhibits tumor cell growth has not been fully understood. Here we report that IFN-gamma up-regulated the expression of Fas and Fas ligand (FasL) on HT29 cells, a human colon adenocarcinoma cell line, and subsequently induced apoptosis of these cells. The kinetics of cell death in IFN-gamma-treated HT29 cells paralleled the increase in the levels of Fas and FasL expression. We further show that IFN-gamma up-regulated the expression of Fas and FasL in STAT1-transfected U3A cells but not in STAT1-deficient U3A cells. Correspondingly, IFN-gamma induced cell death in STAT1-transfected U3A cells but not in STAT1-deficient U3A cells. IFN-gamma-induced cell death was inhibited by caspase-1 inhibitors. Our results suggest that cell growth inhibition by IFN-gamma is due to apoptosis mediated by Fas and FasL interaction.
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Department of General Surgery, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA. xxu@rush.edu
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D020170:Caspase 1; D002455:Cell Division / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000187:drug effects; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D053222:Fas Ligand Protein; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D019073:HT29 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015458:Leukemia, T-Cell / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism*
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D010982:Platelet-Derived Growth Factor; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; D020170:Caspase 1