TY - JOUR
T1 - The Intestinal Wnt/TCF Signature
AU - Van der Flier, Laurens G.
AU - Sabates-Bellver, Jacob
AU - Oving, Irma
AU - Haegebarth, Andrea
AU - De Palo, Mariagrazia
AU - Anti, Marcello
AU - Van Gijn, Marielle E.
AU - Suijkerbuijk, Saskia
AU - Van de Wetering, Marc
AU - Marra, Giancarlo
AU - Clevers, Hans
PY - 2007/2
Y1 - 2007/2
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.
UR - http://www.scopus.com/inward/record.url?scp=33847214547&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2006.08.039
DO - 10.1053/j.gastro.2006.08.039
M3 - Article
C2 - 17320548
AN - SCOPUS:33847214547
SN - 0016-5085
VL - 132
SP - 628
EP - 632
JO - Gastroenterology
JF - Gastroenterology
IS - 2
ER -