Apc gene mutation is associated with a dominant-negative effect upon intestinal cell migration

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 beta-catenin, a molecule important to both cell-cell adhesion and regulati...

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Veröffentlicht in:Cancer research (Chicago, Ill.) Ill.), 1997-11, Vol.57 (22), p.5045-5050
Hauptverfasser: MAHMOUD, N. N, BOOLBOL, S. K, BILINSKI, R. T, MARTUCCI, C, CHADBURN, A, BERTAGNOLLI, M. M
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Sprache:eng
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Zusammenfassung: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 beta-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 beta-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 beta-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.
ISSN:0008-5472
1538-7445