No involvement of beta-catenin gene mutation in gastric carcinomas induced by N-methyl-N-nitrosourea in male F344 rats.
The agent N-methyl-N-nitrosourea (MNU) is a direct acting carcinogen and induces well-differentiated adenocarcinoma on the rat gastric mucosa. In this study, 27 histopathologically verified gastric carcinomas induced in male F344 rats were analyzed for mutations in the N-terminal phosphorylation sites (codons 1-51) of the beta-catenin gene by using polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) assays. In parallel studies, the specific localization of the beta-catenin protein was also examined by immunohistochemical analysis. No mutations in the beta-catenin gene were found in any of 27 gastric carcinomas induced by MNU. Immunohistochemical analysis resulted in the beta-catenin protein to be localized in the plasma membrane but cytoplasmic and/or nuclear accumulation of beta-catenin was not identified in any of these carcinomas. These results suggest that mutations in the beta-catenin gene are less contributory to the development of rat gastric carcinomas induced by MNU. This animal model may provide a system for evaluating the mechanism of human gastric carcinogenesis that is not associated with beta-catenin gene mutations.
Shimizu
Masahito
M
Department of Pathology, Gifu University School of Medicine, 40 Tsukasa-machi, Japan.
Suzui
Masumi
M
Moriwaki
Hisataka
H
Mori
Hideki
H
Yoshimi
Naoki
N
D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics*; D000231:Adenocarcinoma, Papillary / Q000139:chemically induced / Q000235:genetics*; D000818:Animals; D002273:Carcinogens; D002462:Cell Membrane / Q000737:chemistry; D002467:Cell Nucleus / Q000737:chemistry; D003062:Codon; D003593:Cytoplasm / Q000737:chemistry; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D008770:Methylnitrosourea; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D051381:Rats; D011916:Rats, Inbred F344; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000235:genetics*; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D051176:beta Catenin
D002273:Carcinogens; D003062:Codon; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D008565:Membrane Proteins; D015534:Trans-Activators; D051176:beta Catenin; D008770:Methylnitrosourea