β-Catenin mutations and nuclear accumulation during progression of rat stomach adenocarcinomas

Tetsuya Tsukamoto, Masami Yamamoto, Naotaka Ogasawara, Toshikazu Ushijima, Tomoko Nomoto, Hirofumi Fujita, Taijiro Matsushima, Koji Nozaki, Xueyuan Cao, Masae Tatematsu

研究成果: Article査読

22 被引用数 (Scopus)

抄録

Aberrant Wnt/β-catenin signaling caused by mutations in exon 3 of the β-catenin gene has been identified in a number of human malignancies, including stomach cancer. However, studies of mutation frequency have yielded conflicting results, and timing during progression remains largely unknown. In this study, we utilized an animal model to address this question. A total of 20 ACI male rats were treated with N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) in the drinking water and 22 induced differentiated adenocarcinomas were histopathologically and immunohistochemically evaluated for β-catenin localization. Fourteen tumors (63.6%) that showed homogeneous low-grade morphology, preserving cell polarity, were found to harbor β-catenin protein on the cell membranes (M). Eight tumors exhibited regions of high-grade morphology among areas with low-grade morphology, and they were characterized by denser cell growth and loss of cell polarity. Among these 8 tumors, 4 (18.2%) showed cytoplasmic localization (C) of β-catenin in small regions. The remaining 4 tumors (18.2%) contained more dysplastic regions that displayed nuclear (N) β-catenin staining. Analysis of DNA obtained by microdissection demonstrated that all of 4 regions with C staining and 20 with M staining, as well as 17 samples of surrounding normal mucosa (S) had wild-type β-catenin. In contrast, all of 3 regions with N staining featured mutations (3 of 3=100%; N vs. C, P<0.05; N vs. M and N vs. S, P<0.001, Fisher's exact test) in exon 3, at glycine 34, threonine 41, and serine 45, which affected phosphorylation sites. In conclusion, β-catenin mutations appear to be associated with the late progression stage of adenocarcinoma development in rat stomach carcinogenesis, in contrast to the case of colorectal cancers, in which mutations appear to occur in the early stages.

本文言語English
ページ(範囲)1046-1051
ページ数6
ジャーナルCancer science
94
12
DOI
出版ステータスPublished - 01-12-2003
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

フィンガープリント

「β-Catenin mutations and nuclear accumulation during progression of rat stomach adenocarcinomas」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル