Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology*
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Apoptosis / genetics
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Apoptosis / physiology*
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Caspase 1
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Cell Division / drug effects
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Cysteine Endopeptidases / drug effects
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DNA Fragmentation
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DNA, Neoplasm / drug effects
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Epidermal Growth Factor / pharmacology
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Fas Ligand Protein
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Fibroblast Growth Factors / pharmacology
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HT29 Cells / drug effects
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HT29 Cells / metabolism
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Humans
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Interferon-gamma / pharmacology*
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Leukemia, T-Cell / metabolism
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Membrane Glycoproteins / metabolism*
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Platelet-Derived Growth Factor / pharmacology
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STAT1 Transcription Factor
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transfection
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Tumor Necrosis Factor-alpha / pharmacology
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Up-Regulation
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fas Receptor / metabolism*
Substances
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Antineoplastic Agents
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DNA, Neoplasm
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DNA-Binding Proteins
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FASLG protein, human
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Fas Ligand Protein
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Membrane Glycoproteins
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Platelet-Derived Growth Factor
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STAT1 Transcription Factor
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STAT1 protein, human
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Trans-Activators
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Tumor Necrosis Factor-alpha
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fas Receptor
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Fibroblast Growth Factors
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Epidermal Growth Factor
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Interferon-gamma
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Cysteine Endopeptidases
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Caspase 1