title: Mutational analysis of TGF-beta type II receptor, Smad2, Smad3, Smad4, Smad6 and Smad7 genes in colorectal cancer.
abstract: Transforming growth factor-beta(TGF-beta) is known to play an important role in controlling embryonal development, cell proliferation and homeostasis. The purpose of this study is to elucidate the involvement of the TGF-beta pathway in colorectal carcinogenesis. DNA was extracted from 100 patients with colorectal cancer. Then, all coding regions of the TGF-beta type II receptor (TRII) and the genes for Smad2, Smad3, Smad4, Smad6, and Smad7 were analyzed by PCR-SSCP and direct sequencing. Also, a LOH analysis of 18q21, where the Smad2 and Smad4 genes are located, was performed. We detected 11 cases of frameshift mutation in the TRII gene (11%) and 5 cases of point mutations in the Smad4 gene (5.0%); LOH at 18q21 was detected with 33% frequency. No abnormalities were found in the genes for Smad2, Smad3, Smad6, and Smad7. These results suggest that the abnormalities of TRII and Smad4 play an important role inhibiting TGF-beta signaling in colorectal carcinogenesis.
authors.affiliation: Dept. of Surgery 2, Fukushima Medical University School of Medicine, Fukushima City, Japan. fuku@fmu.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Fukushima
authors.forename: M
authors.initials: M
authors.lastname: Mashiko
authors.forename: K
authors.initials: K
authors.lastname: Takita
authors.forename: T
authors.initials: T
authors.lastname: Otake
authors.forename: Y
authors.initials: Y
authors.lastname: Endo
authors.forename: K
authors.initials: K
authors.lastname: Sekikawa
authors.forename: S
authors.initials: S
authors.lastname: Takenoshita
mesh_terms: D001483:Base Sequence; D002887:Chromosomes, Human, Pair 18; D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D016368:Frameshift Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D008969:Molecular Sequence Data; D009154:Mutation; D017354:Point Mutation; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D051905:Smad6 Protein; D051906:Smad7 Protein; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; C497802:SMAD6 protein, human; C497806:SMAD7 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D051905:Smad6 Protein; D051906:Smad7 Protein; D015534:Trans-Activators; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II