Rare mutations of p53, Ki-ras, and beta-catenin genes and absence of K-sam and c-erbB-2 amplification in N-methyl-N'-nitro-N-nitrosoguanidine-induced rat stomach cancers.
Rat stomach cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) have been widely used as a model for human stomach cancers of the differentiated type. However, there has been little information regarding their molecular basis. In this study, we examined the genetic alterations reported in human stomach cancers in 10 rat stomach cancers that had been induced in male ACI/N rats by administering MNNG in the drinking water. One of the 10 cancers had a mutation of the p53 gene at the second position of codon 171 (Val --> Glu). However, none of the 10 cancers had mutations in codons 12, 13, or 61 of Ki-ras or in the N-terminal phosphorylation sites of the beta-catenin gene. Southern blot analysis showed no amplification of K-sam or c-erbB-2 in the seven cancers examined. Finally, we searched for microsatellite alterations in 12 loci in nine cancers, but no alterations were observed. As these genetic alterations are observed in only a minor fraction of human stomach cancers, further analysis of genetic and epigenetic alterations in MNNG-induced rat stomach cancers is needed to disclose the major mechanisms of stomach carcinogenesis.
Hirayama
Y
Y
Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan.
Wakazono
K
K
Yamamoto
M
M
Kitano
M
M
Tatematsu
M
M
Nagao
M
M
Sugimura
T
T
Ushijima
T
T
D000818:Animals; D015139:Blotting, Southern; D003062:Codon / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D005091:Exons / Q000235:genetics; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D008297:Male; D008769:Methylnitronitrosoguanidine; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation; D010766:Phosphorylation; D018807:Polymorphism, Single-Stranded Conformational; D051381:Rats; D011912:Rats, Inbred ACI; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000235:genetics*; D015534:Trans-Activators; D051176:beta Catenin
D003062:Codon; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D017468:Receptors, Fibroblast Growth Factor; D015534:Trans-Activators; D051176:beta Catenin; D008769:Methylnitronitrosoguanidine; C496356:Fgfr2 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2