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. 2005 Aug 19;95(6):487–490. doi: 10.1111/j.1349-7006.2004.tb03237.x

β‐Catenin gene alteration in glandular stomach adenocarcinomas in N‐methyl‐N‐nitrosourea‐treated and Helicobacter pylori‐infected Mongolian gerbils

Xueyuan Cao 1,2, Tetsuya Tsukamoto 1,✉, Koji Nozaki 1,2, Tsutomu Mizoshita 1, Naotaka Ogasawara 1, Harunari Tanaka 1, Yoshiharu Takenaka 1,2, Michio Kaminishi 2, Masae Tatematsu 1
PMCID: PMC11160016  PMID: 15182428

Abstract

The goal of this study was to elucidate whether β‐catenin gene mutations might contribute to glandular stomach carcinogenesis in Helicobacter pylori (H.pylori)‐infected Mongolian gerbils. Firstly, exon 3 of gerbil β‐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. Pep‐tide 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 β‐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) β‐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 β‐catenin localization (7/7). Analysis of exon 3 of the β‐catenin gene demonstrated all tumors with membrane or cytoplasmic staining as well as surrounding normal mucosa (S) to feature wild‐type β‐catenin. In contrast, the lesion with nuclear staining had a mis‐sense 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 β‐catenin may not be a frequent target for mutation in stomach carcinogenesis in MNU+H. pylori‐treated gerbils.

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