title: Alterations in the Smad4 gene in hamster pancreatic duct adenocarcinomas and established cell lines.
abstract: Alterations of the Smad4 gene, identified as a mediator of the transforming growth factor-beta pathway, were investigated in hamster pancreatic duct adenocarcinomas (PDAs) and established cell lines. Female Syrian golden hamsters received 70 mg/kg of N-nitrosobis(2-oxopropyl)amine (BOP) followed by repeated exposure to an augmentation pressure regimen consisting of a choline-deficient diet combined with DL-ethionine then L-methionine and a further administration of 20 mg/kg BOP. A total of 12 PDAs obtained 10 weeks after beginning the experiment and three cell lines established from subcutaneously transplantable PDAs in syngeneic hamsters were examined for mutations using reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) analysis. A mutation was detected in only one PDA (1/12, 8.3%) in the form of an ACC to ATC (Thr to IIe) transition at codon 73; none were detected in the three cell lines. No reduced or increased expression of the Smad4 gene was detected in any case using real-time quantitative RT-PCR. These results suggest that the Smad4 gene might play a role in limited fraction of BOP-induced pancreatic duct carcinogenesis in hamsters.
authors.affiliation: Laboratory of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Technology, Kinki University, Osaka, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Shimizu
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Kitahashi
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Fujii
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsutsumi
authors.forename: Toshio
authors.initials: T
authors.lastname: Mori
authors.forename: Kanya
authors.initials: K
authors.lastname: Honoki
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tsujiuchi
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D006224:Cricetinae; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D008647:Mesocricetus; D009602:Nitrosamines; D018807:Polymorphism, Single-Stranded Conformational; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051901:Smad4 Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D009602:Nitrosamines; D051901:Smad4 Protein; C013622:nitrosobis(2-oxopropyl)amine; D012313:RNA