Title | Apc gene mutation is associated with a dominant-negative effect upon intestinal cell migration. |
Publication Type | Journal Article |
Year of Publication | 1997 |
Authors | Mahmoud NN, Boolbol SK, Bilinski RT, Martucci C, Chadburn A, Bertagnolli MM |
Journal | Cancer Res |
Volume | 57 |
Issue | 22 |
Pagination | 5045-50 |
Date Published | 1997 Nov 15 |
ISSN | 0008-5472 |
Keywords | Analysis of Variance, Animals, Anti-Inflammatory Agents, Non-Steroidal, Apoptosis, beta Catenin, Cell Division, Cell Movement, Cytoskeletal Proteins, Female, Genes, APC, Intestinal Mucosa, Intestine, Small, Mice, Mice, Inbred C57BL, Proliferating Cell Nuclear Antigen, Sulindac, Trans-Activators |
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. |
Alternate Journal | Cancer Res |
PubMed ID | 9371501 |
Grant List | 525435 / / PHS HHS / United States NCI-1R29CA74162-01 / CA / NCI NIH HHS / United States |
Related Faculty:
Amy Chadburn, M.D.