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Cutting Edge: Transgenic Expression of Human MUC1 in IL-10^–/– Mice Accelerates Inflammatory Bowel Disease and Progression to Colon Cancer¹

Pamela L. Beatty^*, Scott E. Plevy, Antonia R. Sepulveda and Olivera J. Finn^2,*

^* Department of Immunology and Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; and Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Cancer Institute Grant CA56103 and Cancer Center Pilot Project CA47904-17.

² Address correspondence and reprint requests to Dr. Olivera J. Finn, Department of Immunology, E1040 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261. Email address: ojfinn{at}pitt.edu

³ Abbreviations used in this paper: IBD, inflammatory bowel disease; UC, ulcerative colitis; CACC, colitis-associated colon cancer; VNTR, variable number of tandem repeats; Tg, transgenic.

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