The Adenomatous Polyposis Coli Gene of the Mouse in Development and Neoplasia
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Excerpt
The intestinal epithelium is the most mitotically active tissue in the adult mammal (see Potten and Morris 1988). Crypts, the sites of mitotic activity, surround regions of differentiation, finger-like villi in the small intestine. As cells migrate away from the proliferative zone, they differentiate to Paneth cells at the base of the crypts or to enterocytes, goblet cells, or enteroendocrine cells in the villi. Overall, in the lifetime of the mouse, the number of mitoses in this tissue is on the order of 1013; in the human it is 1016. The mechanisms that largely protect the intestinal epithelium from the consequences of errors, including mutation and nondisjunction, remain a fundamental mystery (Cairns 1975).
The intestinal epithelium is one of the most common sites for human cancer. Inactivating mutations of the adenomatous polyposis coli gene, APC, are involved in a majority of cases, both sporadic and familial. These include the hereditary...