The Intestinal Wnt/TCF Signature

TY - JOUR

T1 - The Intestinal Wnt/TCF Signature

AU - Flier, L.G. van der

AU - Sabates-Bellver, J.

AU - Oving, I.

AU - Haegebarth, A.

AU - Palo, M. de

AU - Anti, M.

AU - Gijn, M.E. van

AU - Suijkerbuijk, S

AU - Wetering, M. van de

AU - Marra, G.

AU - Clevers, J.C.

N1 - doi:10.1053/j.gastro.2006.08.039

PY - 2007

Y1 - 2007

N2 - 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

AB - 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

M3 - Article

SN - 0016-5085

VL - 132

SP - 628

EP - 632

JO - Gastroenterology

JF - Gastroenterology

ER -