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No involvement of beta-catenin gene mutation in gastric carcinomas induced by N-methyl-N-nitrosourea in male F344 rats.

Abstract
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.
AuthorsMasahito Shimizu, Masumi Suzui, Hisataka Moriwaki, Hideki Mori, Naoki Yoshimi
JournalCancer letters (Cancer Lett) Vol. 195 Issue 2 Pg. 147-52 (Jun 10 2003) ISSN: 0304-3835 [Print] Ireland
PMID12767522 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Carcinogens
  • Codon
  • Ctnnb1 protein, rat
  • Cytoskeletal Proteins
  • DNA, Neoplasm
  • Membrane Proteins
  • Trans-Activators
  • beta Catenin
  • Methylnitrosourea
Topics
  • Adenocarcinoma (chemically induced, genetics)
  • Adenocarcinoma, Papillary (chemically induced, genetics)
  • Animals
  • Carcinogens
  • Cell Membrane (chemistry)
  • Cell Nucleus (chemistry)
  • Codon
  • Cytoplasm (chemistry)
  • Cytoskeletal Proteins (analysis, genetics, physiology)
  • DNA Mutational Analysis
  • DNA, Neoplasm (genetics)
  • Male
  • Membrane Proteins (analysis, genetics)
  • Methylnitrosourea
  • Phosphorylation
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Rats
  • Rats, Inbred F344
  • Stomach Neoplasms (chemically induced, genetics)
  • Trans-Activators (analysis, genetics, physiology)
  • beta Catenin

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