| HINT1 inhibits beta-catenin/TCF4, USF2 and NFkappaB activity in human hepatoma cells. | |
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MedLine Citation:
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PMID: 19089909 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In this study we explored the relevance of Hint, a novel tumor suppressor gene, to human hepatoma. The human hepatoma cell lines Hep3B and HepG2 express very low levels of the HINT1 protein but the Huh7 cells express a relatively high level. In Hep3B and HepG2 cells, but not in Huh7 cells, the promoter region of Hint1 is partially methylated and treatment with 5-azadcdeoxycytidine increased expression of the HINT1 protein and Hint1 mRNA in Hep3B and HepG2 cells. Increased expression of HINT1 in HepG2 cells markedly inhibited their growth. It also inhibited the transcriptional activities of beta-catenin/TCF4, and USF2, and inhibited the expression of endogenous cyclin D1 and TGFbeta2. Furthermore, HINT1 co-immunoprecipitated with USF2 in extracts of Hep2 cells. HINT1 also inhibited NFkappaB transcription factor reporter activity and inhibited translocation of the endogenous p65 protein to the nucleus of HepG2 cells. Therefore, decreased expression of the Hint1 gene through epigenetic silencing may play a role in enhancing the growth of a subset of human hepatoma by increasing the expression of genes controlled by the transcription factors beta-catenin, USF2, and NFkappaB. |
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Authors:
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Lin Wang; Haiyang Li; Yujing Zhang; Regina M Santella; I Bernard Weinstein |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: 124 ISSN: 1097-0215 ISO Abbreviation: Int. J. Cancer Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-02-03 Completed Date: 2009-03-03 Revised Date: 2011-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 1526-34 Citation Subset: IM |
Affiliation:
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Department of Hepatobiliary Surgery, Kunming Medical College, Kunming, China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Blotting, Western Carcinoma, Hepatocellular / genetics*, metabolism Cell Line, Tumor DNA Methylation / genetics DNA-Binding Proteins / genetics, metabolism Enzyme-Linked Immunosorbent Assay Epigenesis, Genetic / genetics Gene Expression Gene Expression Regulation, Neoplastic Humans Immunoprecipitation Liver Neoplasms / genetics*, metabolism NF-kappa B / genetics*, metabolism Nerve Tissue Proteins / genetics*, metabolism Promoter Regions, Genetic / genetics Reverse Transcriptase Polymerase Chain Reaction Transcription Factors / genetics, metabolism Upstream Stimulatory Factors / genetics*, metabolism beta Catenin / genetics*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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ES09089/ES/NIEHS NIH HHS; P30 ES009089-10/ES/NIEHS NIH HHS; R01 ES005116-20/ES/NIEHS NIH HHS; R01 ES005116-21/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; 0/DNA-Binding Proteins; 0/HINT1 protein, human; 0/NF-kappa B; 0/Nerve Tissue Proteins; 0/TCF4 protein, human; 0/Transcription Factors; 0/USF2 protein, human; 0/Upstream Stimulatory Factors; 0/beta Catenin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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