Beta-catenin gene alteration in glandular stomach adenocarcinomas in N-methyl-N-nitrosourea-treated and Helicobacter pylori-infected Mongolian gerbils.
The goal of this study was to elucidate whether beta-catenin gene mutations might contribute to glandular stomach carcinogenesis in Helicobacter pylori (H.pylori)-infected Mongolian gerbils. Firstly, exon 3 of gerbil beta-catenin cDNA, a mutation hot spot, was cloned and sequenced and found to have 89.3% homology with the human form and 95.5% with the rat and mouse forms. Peptide sequence in this region was shown to be 100% conserved in these mammals. Then, 45 stomach adenocarcinomas induced with N-methyl-N-nitrosourea (MNU) plus H. pylori infection and 7 induced with MNU alone were examined for beta-catenin expression by immunohistochemistry and for DNA mutations using a combination of microdissection and PCR-single strand conformation polymorphism analysis. One gastric cancer in the MNU + H. pylori group (2.2%) displayed nuclear (N) beta-catenin localization, 3 (6.7%) showed cytoplasmic (C) distribution in local regions, and 41 (91.1%) demonstrated cell membrane (M) localization. Tumors induced by MNU alone showed only membranous beta-catenin localization (7/7). Analysis of exon 3 of the beta-catenin gene dem-onstrated all tumors with membrane or cytoplasmic staining as well as surrounding normal mucosa (S) to feature wild-type beta-catenin. In contrast, the lesion with nuclear staining had a missense mutation at codon 34 [GAC (Gly) --> GAA (Glu)] in exon 3 (1/1 = 100%, N vs. M, P < 0.05; and N vs. S, P < 0.05). In conclusion, these results suggest that beta-catenin may not be a frequent target for mutation in stomach carcinogenesis in MNU + H. pylori-treated gerbils.
Cao
Xueyuan
X
Division of Oncological Pathology, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya, Aichi 464-8681, Japan.
Tsukamoto
Tetsuya
T
Nozaki
Koji
K
Mizoshita
Tsutomu
T
Ogasawara
Naotaka
N
Tanaka
Harunari
H
Takenaka
Yoshiharu
Y
Kaminishi
Michio
M
Tatematsu
Masae
M
D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics*; D005091:Exons; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori; D008297:Male; D008770:Methylnitrosourea; D008969:Molecular Sequence Data; D009154:Mutation; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics*; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics*; D051176:beta Catenin
D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D008770:Methylnitrosourea