36种胃肠道和肝癌细胞中β-连环蛋白/T细胞因子信号通路的分析
Analysis of the beta-catenin/T cell factor signaling pathway in 36 gastrointestinal and liver cancer cells.
作者信息
Ikenoue Tsuneo, Ijichi Hideaki, Kato Naoya, Kanai Fumihiko, Masaki Tsutomu, Rengifo William, Okamoto Makoto, Matsumura Masayuki, Kawabe Takao, Shiratori Yasushi, Omata Masao
机构信息
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
出版信息
Jpn J Cancer Res. 2002 Nov;93(11):1213-20. doi: 10.1111/j.1349-7006.2002.tb01226.x.
We investigated the frequency and mechanism of beta-catenin/T cell factor (Tcf) signaling activation in a panel of 36 human gastrointestinal and liver cancer cell lines. Reporter assay and electrophoretic mobility shift assay revealed that the beta-catenin/Tcf signaling was upregulated in 12 of 12 (100%) colorectal, 5 of 8 (68%) gastric, 2 of 7 (29%) hepatic, and none of 9 pancreatic cancer cell lines. The activation of the pathway was mainly due to the mutation of adenomatous polyposis coli (APC) or beta-catenin, and Tcf-4 was highly expressed in these cell lines with upregulated signaling. Nuclear beta-catenin was observed not only in the signaling-activated cell lines, but also in 14 of 25 (56%) primary gastric cancers, 15 of 20 (75%) colon cancers, 5 of 19 (26%) hepatocellular carcinomas, and none of 13 pancreatic cancers. The presence of signaling-upregulated gastric cancer cell lines with intact APC and beta-catenin suggests the involvement of other mechanisms than mutations of APC or beta-catenin.
我们在一组36个人类胃肠道及肝癌细胞系中研究了β-连环蛋白/T细胞因子（Tcf）信号激活的频率和机制。报告基因检测和电泳迁移率变动分析显示，β-连环蛋白/Tcf信号在12株结直肠癌细胞系中的12株（100%）、8株胃癌细胞系中的5株（68%）、7株肝癌细胞系中的2株（29%）以及9株胰腺癌细胞系中均上调。该信号通路的激活主要归因于腺瘤性息肉病基因（APC）或β-连环蛋白的突变，并且Tcf-4在这些信号上调的细胞系中高表达。核β-连环蛋白不仅在信号激活的细胞系中被观察到，在25例原发性胃癌中的14例（56%）、20例结肠癌中的15例（75%）、19例肝细胞癌中的5例（26%）以及13例胰腺癌中均未观察到。APC和β-连环蛋白完整的信号上调胃癌细胞系的存在提示除了APC或β-连环蛋白突变外还涉及其他机制。
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