title: Apc gene mutation is associated with a dominant-negative effect upon intestinal cell migration.
abstract: 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.
authors.affiliation: The New York Hospital-Cornell University Medical Center, New York 10021, USA.
authors.forename: N N
authors.initials: NN
authors.lastname: Mahmoud
authors.forename: S K
authors.initials: SK
authors.lastname: Boolbol
authors.forename: R T
authors.initials: RT
authors.lastname: Bilinski
authors.forename: C
authors.initials: C
authors.lastname: Martucci
authors.forename: A
authors.initials: A
authors.lastname: Chadburn
authors.forename: M M
authors.initials: MM
authors.lastname: Bertagnolli
mesh_terms: 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
chemical_list: 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