Adenomatous polyposis coli-deficient zebrafish are susceptible to digestive tract neoplasia
Adenomatous polyposis coli-deficient zebrafish are susceptible to digestive tract neoplasia
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DOI：
10.1038/sj.embor.7400638
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发表时间：
2006-04-01
期刊：
影响因子：
7.7
通讯作者：
Clevers, HC
中科院分区：
文献类型：
--
作者：
Haramis, APG;Hurlstone, A;Clevers, HC
肿瘤抑制基因腺瘤性结肠息肉病（APC）的截短组成性激活Wnt/β-连环蛋白信号通路。该事件构成了人类散发性结直肠癌的主要转化事件。此外，在APC中携带生殖系截断突变的人或小鼠发展出大量的肠腺瘤。在这里，我们报告说，斑马鱼是一个截短APC突变杂合自发发展肠，肝和胰腺肿瘤是高度增殖，积累β-连环蛋白和表达Wnt靶基因。用化学致癌物7，12二甲基苯并[a]蒽治疗加速了这些病变的诱导。这些观察结果使APC突变的斑马鱼成为研究消化道癌症的真正模型。
Truncation of the tumour suppressor adenomatous polyposis coli (APC) constitutively activates the Wnt/beta-catenin signalling pathway. This event constitutes the primary transforming event in sporadic colorectal cancer in humans. Moreover, humans or mice carrying germline truncating mutations in APC develop large numbers of intestinal adenomas. Here, we report that zebrafish that are heterozygous for a truncating APC mutation spontaneously develop intestinal, hepatic and pancreatic neoplasias that are highly proliferative, accumulate beta-catenin and express Wnt target genes. Treatment with the chemical carcinogen 7,12dimethylbenz[a] anthracene accelerates the induction of these lesions. These observations establish apc- mutant zebrafish as a bona fide model for the study of digestive tract cancer.