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- Title
Intestinal tumor progression is promoted by decreased apoptosis and dysregulated Wnt signaling in Ceacam1<sup>−/−</sup> mice.
- Authors
Leung, N; Turbide, C; Balachandra, B; Marcus, V; Beauchemin, N
- Abstract
The carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is downregulated in colonic and intestinal hyperplastic lesions as well as in other cancers, where it functions as a tumor suppressor. To investigate the functions of CEACAM1 in the normal intestine and in intestinal tumors, we generated a compound knockout mouse model and examined both Ceacam1−/− and Apc1638N/+:Ceacam1−/− mice. Ceacam1−/− intestinal cells exhibited a significant decrease in apoptosis, with no change in proliferation or migration, however. Compound Apc1638N/+:Ceacam1−/− mice demonstrated an increase in intestinal tumor multiplicity and tumor progression. Increases in intussusceptions and desmoid lesions were also observed. We have shown that CEACAM1-L associates with β-catenin by co-immunoprecipitation and colocalization in CEACAM1-L-transfected CT26 and CT51 mouse colon carcinoma cells. Ceacam1−/− enterocytes displayed decreased glycogen synthase kinase 3-β activity with corresponding nuclear localization of β-catenin. Increased T-cell factor/Lef transcriptional activity was observed in CEACAM1-null CT51 colonic cells and in Caco2 colon cancer cells in which CEACAM1 was downregulated. A significant increased expression in c-Myc and cyclin D1 targets of the Wnt signaling pathway was also revealed in the Ceacam1−/− intestine. CEACAM1 therefore actively participates in Wnt signaling in intestinal cells and its downregulation in intestinal tissue contributes to malignancy by augmenting tumor multiplicity and progression.Oncogene (2008) 27, 4943–4953; doi:10.1038/onc.2008.136; published online 5 May 2008
- Subjects
PRECANCEROUS conditions; TUMORS; INTESTINES; APOPTOSIS; COLON (Anatomy)
- Publication
Oncogene, 2008, Vol 27, Issue 36, p4943
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/onc.2008.136