Abstract
TGF-beta is a negative regulator of liver growth. Smad family of genes, as mediators of TGF-beta pathway, are candidate tumor suppressor genes in hepatocellular carcinoma (HCC). We studied 35 HCC and non-tumour liver tissues for possible mutations in Smad2 and Smad4 genes. Three tumours displayed somatic mutations; two in Smad4 (Asp332Gly and Cys401Arg) and one in Smad2 (Gln407Arg) genes. All three mutations were A:T --> G:C transitions suspected to result from oxidative stress as observed in mitochondrial DNA. These observation demonstrate that TGF-beta pathway is altered in hepatocellular carcinoma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Base Sequence
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Carcinoma, Hepatocellular / genetics*
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Carcinoma, Hepatocellular / metabolism
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Gene Frequency
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Genes, Tumor Suppressor
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Humans
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Liver Neoplasms / genetics*
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Liver Neoplasms / metabolism
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Molecular Sequence Data
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Mutation*
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Signal Transduction
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Smad2 Protein
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Smad4 Protein
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Trans-Activators / genetics*
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Trans-Activators / metabolism
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Transforming Growth Factor beta / metabolism
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Tumor Cells, Cultured
Substances
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DNA-Binding Proteins
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SMAD2 protein, human
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SMAD4 protein, human
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Smad2 Protein
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Smad4 Protein
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Trans-Activators
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Transforming Growth Factor beta