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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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1997-11, Vol.57 (22), p.5045-5050
Main Authors: MAHMOUD, N. N, BOOLBOL, S. K, BILINSKI, R. T, MARTUCCI, C, CHADBURN, A, BERTAGNOLLI, M. M
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Apoptosis - drug effects
beta Catenin
Biological and medical sciences
Cell Division - drug effects
Cell Division - genetics
Cell Movement - drug effects
Cell Movement - genetics
Cytoskeletal Proteins - metabolism
Female
Gastroenterology. Liver. Pancreas. Abdomen
Genes, APC - genetics
Intestinal Mucosa - cytology
Intestinal Mucosa - drug effects
Intestinal Mucosa - metabolism
Intestine, Small - cytology
Intestine, Small - drug effects
Intestine, Small - metabolism
Medical sciences
Mice
Mice, Inbred C57BL
Proliferating Cell Nuclear Antigen - metabolism
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Sulindac - pharmacology
Trans-Activators
Tumors
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Summary: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