Abstract
Interferon-gamma (IFN-gamma) induces growth arrest and apoptosis of tumor cells but the mechanisms for these functions are unknown. Recently, gut-enriched krüppel-like factor (GKLF) was found to possess similar biological properties. Treatment of HT-29 cells with IFN-gamma inhibited cell proliferation and induced apoptosis, the effect was found to associate with GKLF expression. IFN-gamma stimulates GKLF mRNA and protein levels in a dose- and time-dependent manner and this process is independent of p53, occurs rapidly and does not require de novo protein synthesis indicating that GKLF is an immediate-early IFN-gamma-responsive gene. Moreover, overexpression of GKLF results in similar effect as IFN-gamma suggesting that GKLF may function as a downstream target of IFN-gamma.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Blotting, Western
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Cell Division / drug effects
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Colonic Neoplasms / genetics
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Colonic Neoplasms / metabolism*
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Colonic Neoplasms / pathology
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DNA-Binding Proteins*
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Dactinomycin / pharmacology
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Dose-Response Relationship, Drug
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Humans
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Interferon-gamma / pharmacology*
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Kinetics
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Kruppel-Like Factor 4
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Kruppel-Like Transcription Factors
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Protein Biosynthesis / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Substrate Specificity
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Transcription Factors / genetics*
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Transcription Factors / metabolism*
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Transfection
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / physiology
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Up-Regulation / drug effects*
Substances
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Antineoplastic Agents
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DNA-Binding Proteins
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KLF4 protein, human
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Kruppel-Like Factor 4
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Kruppel-Like Transcription Factors
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RNA, Messenger
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Transcription Factors
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Tumor Suppressor Protein p53
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Dactinomycin
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Interferon-gamma