Cutting edge:: Transgenic expression of human MUC1 in IL-10-/- mice accelerates inflammatory bowel disease and progression to colon cancer
Cutting edge:: Transgenic expression of human MUC1 in IL-10-/- mice accelerates inflammatory bowel disease and progression to colon cancer
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DOI：
10.4049/jimmunol.179.2.735
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发表时间：
2007-07-15
影响因子：
4.4
通讯作者：
Finn, Olivera J.
中科院分区：
文献类型：
--
作者：
Beatty, Pamela L.;Plevy, Scott E.;Finn, Olivera J.
上皮细胞MUC1在人上皮腺癌中异常表达，其功能是调节免疫反应和致癌基因。MUC1通常在健康的结肠上皮中表达水平较低，但据报道在人类炎症性肠病（IBD）中过度表达，因此可能在调节慢性炎症及其向结肠炎相关结肠癌的进展中发挥重要作用。对IBD和结肠炎相关结肠癌的免疫生物学和病理学的研究已经在各种小鼠模型中进行了，但由于小鼠和人类分子之间的同源性较低，没有一个能够适当地解决MUC1的作用。我们报道，与IL-10（-/-）小鼠相比，IL-10（-/-）小鼠，一种被广泛接受的IBD小鼠模型，与人类MUC1转基因小鼠杂交，发生MUC1(+) IBD，其特征是发病年龄更早，炎症评分更高，结肠癌发病率和数量更高。
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.