Abstract
Here we show that in contrast to other cancer types, tumor necrosis factor (TNF)-alpha suppresses YKL-40 expression in glioma cell lines in a nuclear factor kappaB (NF-kappaB) dependent manner. Even though TNF-alpha causes recruitment of p65 and p50 subunits of NF-kappaB to the YKL-40 promoter in all cell types, recruitment of histone deacetylases (HDAC)-1 and -2, and a consequent deacetylation of histone H3 at the YKL-40 promoter occurs only in glioma cells. Importantly, using chromatin immunoprecipitation assays in frozen glioblastoma multiforme tissues, we show that YKL-40 levels decrease consistent with HDAC1 recruitment despite high levels of nuclear p-p65. This study presents a paradigm for NF-kappaB regulation of one of its targets in a strict cell type specific manner.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Adipokines
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Cell Line, Tumor
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Chitinase-3-Like Protein 1
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Chromatin Immunoprecipitation
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Down-Regulation
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Gene Expression Regulation, Neoplastic*
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Glioma / genetics
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Glioma / metabolism*
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Glycoproteins / genetics*
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Histone Deacetylase 1
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Histone Deacetylase 2
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Histone Deacetylases / metabolism*
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Histones / metabolism
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Humans
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Lectins
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NF-kappa B / metabolism*
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NF-kappa B p50 Subunit / metabolism
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Promoter Regions, Genetic
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Repressor Proteins / metabolism*
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Transcription Factor RelA / metabolism
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Tumor Necrosis Factor-alpha / pharmacology
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Tumor Necrosis Factor-alpha / physiology
Substances
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Adipokines
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CHI3L1 protein, human
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Chitinase-3-Like Protein 1
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Glycoproteins
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Histones
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Lectins
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NF-kappa B
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NF-kappa B p50 Subunit
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Repressor Proteins
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Transcription Factor RelA
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Tumor Necrosis Factor-alpha
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HDAC1 protein, human
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Histone Deacetylase 1
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Histone Deacetylase 2
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Histone Deacetylases