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.
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 humanadenomas and adenocarcinomas vs normal colonic epithelium were obtained. RESULTS: Expression analyses of approximately 80 genes common between these data sets were performed in a murineadenoma 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.
Authors: Peter Balaz; Jens Plaschke; Stefan Krüger; Heike Görgens; Hans K Schackert Journal: Int J Colorectal Dis Date: 2010-06-08 Impact factor: 2.571
Authors: Catrina E King; Miriam Cuatrecasas; Antoni Castells; Antonia R Sepulveda; Ju-Seog Lee; Anil K Rustgi Journal: Cancer Res Date: 2011-04-21 Impact factor: 12.701
Authors: Julian Heuberger; Frauke Kosel; Jingjing Qi; Katja S Grossmann; Klaus Rajewsky; Walter Birchmeier Journal: Proc Natl Acad Sci U S A Date: 2014-02-18 Impact factor: 11.205
Authors: Felipe De Sousa E Melo; Xin Wang; Marnix Jansen; Evelyn Fessler; Anne Trinh; Laura P M H de Rooij; Joan H de Jong; Onno J de Boer; Ronald van Leersum; Maarten F Bijlsma; Hans Rodermond; Maartje van der Heijden; Carel J M van Noesel; Jurriaan B Tuynman; Evelien Dekker; Florian Markowetz; Jan Paul Medema; Louis Vermeulen Journal: Nat Med Date: 2013-04-14 Impact factor: 53.440