The Glucocorticoid Receptor in Intestinal Epithelial Cells Alleviates Colitis and Associated Colorectal Cancer in Mice
Chiara Muzzi, Norika Watanabe, Eric Twomey, Garrit K. Meers, Holger M. Reichardt, Hanibal Bohnenberger, Sybille D. Reichardt
Abstract
BACKGROUND & AIMS: mice, which carry an inducible deletion of the glucocorticoid receptor in intestinal epithelial cells. METHODS: Colitis and colitis-associated colorectal cancer were induced by administration of dextran sulfate sodium and azoxymethane in mice. Clinical parameters, epithelial permeability and tumor development were monitored during disease progression. Colon tissue, lamina propria cells and intestinal epithelial cells were examined by gene expression analyses, flow cytometry, histopathology, and immunohistochemistry. RESULTS: mice also enhanced associated tumorigenesis, resulting in a higher number and larger size of tumors in the colon. CONCLUSIONS: Our results reveal an important role of intestinal epithelial cells as targets of glucocorticoid action in inflammatory bowel disease and suggest that the efficacy with which colitis is kept at bay directly affects the progression of colorectal cancer.