Abstract
P300 impacts the transcription of several genes involved in biological behavior of human malignancies including hepatocellular carcinomas (HCC). We found p300 is highly expressed in 47% of surgically resected HCC specimens by immunohistochemistry, which correlated with advanced TNM staging (P = 0.034), vascular invasion (P = 0.036), intrahepatic metastasis (P = 0.001) and shortened overall survival (P = 0.028). In vitro study, knocking down of p300 expression in hepatoma cells recovered E-cadherin expression, inhibited the translocation of beta (β)-catenin into the nuclei, decreased cyclin D1 activity and suppressed the migration/invasion of HCC cells. Furthermore, suppression of p300 led to down-regulation of epithelial-mesenchymal transition (EMT)-related molecules such as Snail, Twist and HIF-1 alpha. These observations suggest that p300 contributes to the EMT-related progression of HCCs.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Apoptosis / physiology
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Biomarkers, Tumor / biosynthesis
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Biomarkers, Tumor / genetics
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Cadherins / biosynthesis
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Cadherins / genetics
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / metabolism*
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Carcinoma, Hepatocellular / pathology*
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Carcinoma, Hepatocellular / surgery
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Cell Dedifferentiation / physiology
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Cell Line, Tumor
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Cyclin D1 / biosynthesis
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Cyclin D1 / genetics
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Down-Regulation
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E1A-Associated p300 Protein / biosynthesis*
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E1A-Associated p300 Protein / genetics
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Epithelial-Mesenchymal Transition
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Female
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Humans
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Immunoblotting
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Immunohistochemistry
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Liver Neoplasms / genetics
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Liver Neoplasms / metabolism*
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Liver Neoplasms / pathology*
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Liver Neoplasms / surgery
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Male
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Middle Aged
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Neoplasm Staging
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RNA, Small Interfering / administration & dosage
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RNA, Small Interfering / genetics
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Survival Analysis
Substances
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Biomarkers, Tumor
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CCND1 protein, human
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Cadherins
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RNA, Small Interfering
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Cyclin D1
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E1A-Associated p300 Protein
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EP300 protein, human