Gene expression profiles of intestinal tumors originating from different cell compartments

Introduction of mutations into intestinal stem cells leads to tumorigenesis, therefore intestinal stem cells are believed to function as cell of origin of intestinal tumors. However in the case of additional protumorigenic stimuli differentiated cells can dedifferentiate and can also give rise to intestinal tumors. Expression of stabilized β-catenin (CtnnbloxEx3/+) and mutant KrasG12D/+ in all the intestinal cells by using Cre recombinase driven by the villin promoter (VilCreER) leads to rapid transformation and tumorigenesis. However, when the same mutations are introduced only into the differentited cell by the help of Xbp1sCreER mice also develop tumors. In this study we wished to investigate if the cell of origin would impact the gene expression profile of intestinal tumors. Therefore we compared the gene expression profiles of early stage tumors derived from VilCreER CtnnbloxEx3/+ KrasG12D/+ mice and early stage tumors derived from Xbp1sCreER CtnnbloxEx3/+ KrasG12D/+ mice by microarray. Mice were treated with 1 mg Tamoxifen on five consecutive days to induce the activity of the Cre recombinase and the expression of CtnnbloxEx3/+ and KrasG12D/+. Both VilCreER CtnnbloxEx3/+ KrasG12D/+ and Xbp1sCreER CtnnbloxEx3/+ KrasG12D/+ mice were sacrificed when early intestinal tumors were already present (day 7 for VilCreER CtnnbloxEx3/+ KrasG12D/+ and day 21 for Xbp1sCreER CtnnbloxEx3/+ KrasG12D/+). RNA was extracted from isolated epithelial cell extracts of both genotypes.