Abstract
Ligand activation of peroxisome proliferator-activated receptor gamma (PPARgamma) has been reported to induce growth inhibition and apoptosis in various cancers including hepatocellular carcinoma (HCC). However, the effect of hepatitis B virus X protein (HBx) on PPARgamma activation has not been characterized in hepatitis B virus (HBV)-associated HCC. Herein, we demonstrated that HBx counteracted growth inhibition caused by PPARgamma ligand in HBx-associated HCC cells. We found that HBx bound to DNA binding domain of PPARgamma and HBx/PPARgamma interaction blocked nuclear localization and binding to recognition site of PPARgamma. HBx significantly suppressed a PPARgamma-mediated transactivation. These results suggest that HBx modulates PPARgamma function through protein-protein interaction.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae
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Apoptosis / drug effects
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Base Sequence
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Carcinoma, Hepatocellular / pathology
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Carcinoma, Hepatocellular / virology
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Cell Division / drug effects
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Cell Line
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DNA Primers
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Genes, Reporter
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Genetic Vectors
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Green Fluorescent Proteins
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Hepatitis B Antigens / chemistry
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Hepatitis B Antigens / pharmacology
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Humans
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Ligands
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Liver Neoplasms / pathology
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Liver Neoplasms / virology
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Luminescent Proteins / genetics
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Protein Transport / drug effects
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Receptors, Cytoplasmic and Nuclear / chemistry
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Receptors, Cytoplasmic and Nuclear / drug effects
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / drug effects
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Recombinant Fusion Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Trans-Activators / chemistry
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Trans-Activators / metabolism
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Trans-Activators / pharmacology*
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Transcription Factors / chemistry
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Transcription Factors / drug effects
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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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Viral Regulatory and Accessory Proteins
Substances
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DNA Primers
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Hepatitis B Antigens
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Ligands
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Luminescent Proteins
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Receptors, Cytoplasmic and Nuclear
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Recombinant Fusion Proteins
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Trans-Activators
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Transcription Factors
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Viral Regulatory and Accessory Proteins
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hepatitis B virus X protein
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Green Fluorescent Proteins