Apc-associated intestinal tumor formation appears to require functional loss of both Apc alleles. Apc has, therefore, been classified as a tumor suppressor gene. Loss of APC protein function results in increased intracellular β-catenin, a molecule important to both cell-cell adhesion and regulation of cellular growth. In mice bearing a germ-line Apc mutation, we found that enterocyte β-catenin expression was also increased in histologically normal intestinal mucosa. Enterocyte crypt-villus migration was decreased by 25%, and treatment of Min/+ animals with sulindac sulfide normalized both β-catenin expression and enterocyte migration. Our data suggest that alterations in enterocyte migration occur in cells bearing a single mutant Apc allele, and that sulindac sulfide may normalize enterocyte growth in these cells.


Supported by American Cancer Society Grant ACS CDA-95010-95, National Cancer Institute Grant NCI-1R29CA74162-01, and a grant from the Alice Bohmfalk Charitable Trust (all to M. M. B.) and National Institute of Health NIH Surgical Oncology Research Training Grant 525435 and a grant from the Cancer Research Foundation of America (both to N. N. M.).

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