Cutting edge: transgenic expression of human MUC1 in IL-10−/− mice accelerates inflammatory bowel disease and progression to colon cancer

PL Beatty, SE Plevy, AR Sepulveda… - The Journal of …, 2007 - journals.aai.org
PL Beatty, SE Plevy, AR Sepulveda, OJ Finn
The Journal of Immunology, 2007journals.aai.org
Epithelial cell MUC1 is aberrantly expressed on human epithelial adenocarcinomas where it
functions as a regulator of immune responses and an oncogene. Normally expressed at low
levels in healthy colonic epithelium, MUC1 was reported to be overexpressed in human
inflammatory bowel disease (IBD) and thus may be expected to play an important role in
regulating chronic inflammation and its progression to colitis-associated colon cancer.
Studies in the immunobiology and pathology of IBD and colitis-associated colon cancer …
Abstract
Epithelial cell MUC1 is aberrantly expressed on human epithelial adenocarcinomas where it functions as a regulator of immune responses and an oncogene. Normally expressed at low levels in healthy colonic epithelium, MUC1 was reported to be overexpressed in human inflammatory bowel disease (IBD) and thus may be expected to play an important role in regulating chronic inflammation and its progression to colitis-associated colon cancer. Studies in the immunobiology and pathology of IBD and colitis-associated colon cancer have been done in various mouse models but none could properly address the role of MUC1 due to low homology between the mouse and the human molecule. We report that IL-10−/− mice, a widely accepted mouse model of IBD, crossed to human MUC1-transgenic mice, develop MUC1+ IBD characterized by an earlier age of onset, higher inflammation scores, and a much higher incidence and number of colon cancers compared with IL-10−/− mice.
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