Abstract
A thorough understanding of histone acetyltransferase CBP/p300-mediated regulation of gene expression and cell growth is essential to identify mechanisms relevant to the development of histone deacetylase (HDAC) inhibitor-based preventive and therapeutic strategies. We found that knockdown of CBP/p300 interacting coactivator with glutamic acid/aspartic acid-rich tail 2 (CITED2) increased colon cancer cell invasiveness in vitro. Gene expression profiling revealed that CITED2 knockdown induced matrix metalloproteinase-13 (MMP-13) gene expression in colon cancer cells. Butyrate, a naturally occurring HDAC inhibitor, induced CITED2 expression and downregulated MMP-13 expression in RKO cells. Additionally, ectopic expression of CITED2 arrested RKO cell growth. Thus, CITED2 regulates colon cancer invasion and might be a target for HDAC inhibitor-based intervention of colon cancer.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Butyrates / pharmacology
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Colonic Neoplasms / enzymology
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Colonic Neoplasms / genetics
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Colonic Neoplasms / pathology*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Down-Regulation / drug effects
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E1A-Associated p300 Protein / metabolism*
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Matrix Metalloproteinase 13 / genetics
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Matrix Metalloproteinase 13 / metabolism
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Neoplasm Invasiveness
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Up-Regulation / drug effects
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beta Catenin / metabolism
Substances
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Butyrates
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CITED2 protein, human
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DNA-Binding Proteins
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Repressor Proteins
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Trans-Activators
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beta Catenin
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E1A-Associated p300 Protein
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EP300 protein, human
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Matrix Metalloproteinase 13