Sasaki Y, Morimoto I, Kusano M, Hosokawa M, Itoh F, Yanagihara K, Imai K, Tokino T
Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University School of Medicine, Sapporo, Japan.
Tumour Biol. 2001 Mar-Apr;22(2):123-30. doi: 10.1159/000050606.
Previous studies reported that mutation of the adenomatous polyposis coli (APC) gene was not observed in the majority of gastric cancers. To evaluate the role of the APC/beta-catenin/Tcf pathway, we analyzed mutations in the beta-catenin gene and the accumulation of beta-catenin protein in gastric carcinomas. An interstitial deletion spanning exon 3 of the beta-catenin gene was observed in 1 of 13 gastric cancer cell lines. No missense mutation was found in these 13 cell lines. Nuclear and/or cytoplasmic localization of beta-catenin was observed in 16 of 70 primary gastric carcinomas by immunohistochemistry, while we found no mutations in exon 3 in 35 carcinoma tissues available for PCR amplification. Our findings suggest that somatic mutations of the beta-catenin gene are rare in human gastric carcinomas and that accumulation of normal beta-catenin protein in a subset of gastric cancers may be due to other mechanisms of its activation.
先前的研究报道,在大多数胃癌中未观察到腺瘤性息肉病大肠杆菌(APC)基因的突变。为了评估APC/β-连环蛋白/Tcf信号通路的作用,我们分析了β-连环蛋白基因的突变以及β-连环蛋白在胃癌中的积累情况。在13个胃癌细胞系中的1个中观察到跨越β-连环蛋白基因第3外显子的间质缺失。在这13个细胞系中未发现错义突变。通过免疫组织化学在70例原发性胃癌中的16例中观察到β-连环蛋白的核和/或细胞质定位,而在35例可用于PCR扩增的癌组织中未发现第3外显子的突变。我们的研究结果表明,β-连环蛋白基因的体细胞突变在人类胃癌中很少见,并且在一部分胃癌中正常β-连环蛋白的积累可能是由于其激活的其他机制。