title: Mutational analysis of the Smad6 and Smad7 genes in hepatocellular carcinoma.
abstract: Resistance to the transforming growth factor-beta (TGF-beta) is a frequently found phenotype in human malignancies. The recent identification of Smad6 and Smad7, both anti-Smads which inhibit TGF-beta signaling, raises a possibility that constitutive activation of the anti-Smads by a somatic mutation may impair the TGF-beta signaling pathway. We tested this hypothesis by screening the entire coding sequences of these anti-Smads for mutations in 52 hepatocellular carcinoma (HCC) samples using polymerase chain reaction - single strand conformation polymorphism analysis. We detected no mutations, but found 3 single nucleotide polymorphisms (SNPs) in the Smad6 gene and 2 SNPs in the Smad7 gene. These results suggest that mutations of the Smad6 and Smad7 genes are not the main cause of the TGF-beta resistance in human HCC.
authors.affiliation: Second Department of Surgery, Gunma University Faculty of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kawate
authors.forename: S
authors.initials: S
authors.lastname: Ohwada
authors.forename: K
authors.initials: K
authors.lastname: Hamada
authors.forename: T
authors.initials: T
authors.lastname: Koyama
authors.forename: S
authors.initials: S
authors.lastname: Takenoshita
authors.forename: Y
authors.initials: Y
authors.lastname: Morishita
authors.forename: K
authors.initials: K
authors.lastname: Hagiwara
mesh_terms: D000483:Alleles; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D051905:Smad6 Protein; D051906:Smad7 Protein; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497802:SMAD6 protein, human; C497806:SMAD7 protein, human; D051905:Smad6 Protein; D051906:Smad7 Protein; D015534:Trans-Activators