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 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.
Mahmoud
N N
NN
The New York Hospital-Cornell University Medical Center, New York 10021, USA.
Boolbol
S K
SK
Bilinski
R T
RT
Martucci
C
C
Chadburn
A
A
Bertagnolli
M M
MM
D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D017491:Genes, APC / Q000235:genetics*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D013467:Sulindac / Q000494:pharmacology; D015534:Trans-Activators; D051176:beta Catenin
D000894:Anti-Inflammatory Agents, Non-Steroidal; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D018809:Proliferating Cell Nuclear Antigen; D015534:Trans-Activators; D051176:beta Catenin; D013467:Sulindac