Van der Flier Laurens G, Sabates-Bellver Jacob, Oving Irma, Haegebarth Andrea, De Palo Mariagrazia, Anti Marcello, Van Gijn Marielle E, Suijkerbuijk Saskia, Van de Wetering Marc, Marra Giancarlo, Clevers Hans
Hubrecht Institute, Netherlands Institute for Developmental Biology and Centre for Biomedical Genetics, Utrecht, The Netherlands.
Gastroenterology. 2007 Feb;132(2):628-32. doi: 10.1053/j.gastro.2006.08.039. Epub 2006 Aug 18.
BACKGROUND & AIMS: In colorectal cancer, activating mutations in the Wnt pathway transform epithelial cells through the inappropriate expression of a TCF4 target gene program, which is physiologically expressed in intestinal crypts.
We have now performed an exhaustive array-based analysis of this target gene program in colorectal cancer cell lines carrying an inducible block of the Wnt cascade. Independently, differential gene-expression profiles of human adenomas and adenocarcinomas vs normal colonic epithelium were obtained.
Expression analyses of approximately 80 genes common between these data sets were performed in a murine adenoma model. The combined data sets describe a core target gene program, the intestinal Wnt/TCF signature gene set, which is responsible for the transformation of human intestinal epithelial cells.
The genes were invariably expressed in adenomas, yet could be subdivided into 3 modules, based on expression in distinct crypt compartments. A module of 17 genes was specifically expressed at the position of the crypt stem cell.
在结直肠癌中，Wnt信号通路中的激活突变通过不适当表达一种在生理状态下于肠隐窝中表达的TCF4靶基因程序来转化上皮细胞。
我们现在对携带Wnt级联反应诱导性阻断的结直肠癌细胞系中的该靶基因程序进行了详尽的基于阵列的分析。独立地，获取了人类腺瘤和腺癌与正常结肠上皮的差异基因表达谱。
在小鼠腺瘤模型中对这些数据集中约80个共同基因进行了表达分析。合并后的数据集描述了一个核心靶基因程序，即肠道Wnt/TCF特征基因集，其负责人类肠道上皮细胞的转化。
这些基因在腺瘤中总是表达，但根据在不同隐窝区室中的表达情况可分为3个模块。一个由17个基因组成的模块在隐窝干细胞位置特异性表达。
