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Updated: Jul 5, 2026

In vitro Organoid Culture of Primary Mouse Colon Tumors
Published on: May 17, 2013
Intestinal tumor progression is promoted by decreased apoptosis and dysregulated Wnt signaling in Ceacam1-/- mice
N Leung1, C Turbide, B Balachandra
1McGill Cancer Centre, McGill University, Montreal, Québec, Canada.
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 Apc(1638N/+):Ceacam1(-/-) mice. Ceacam1(-/-) intestinal cells exhibited a significant decrease in apoptosis, with no change in proliferation or migration, however. Compound Apc(1638N/+):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 beta-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-beta activity with corresponding nuclear localization of beta-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.
Insights
Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) loss reduces apoptosis, promoting intestinal tumor growth. CEACAM1 deficiency activates Wnt signaling, increasing tumor multiplicity and progression in mice.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) acts as a tumor suppressor, often downregulated in cancers.
- Its role in normal intestinal function and tumorigenesis requires further elucidation.
Purpose of the Study:
- To investigate the function of CEACAM1 in the normal intestine and in intestinal tumors.
- To determine the impact of CEACAM1 deficiency on intestinal cell apoptosis, proliferation, and migration.
- To analyze the effect of CEACAM1 loss on Wnt signaling pathways and tumor development.
Main Methods:
- Generation of compound knockout mouse models (Ceacam1(-/-) and Apc(1638N/+):Ceacam1(-/-)).
- Assessment of intestinal cell apoptosis, proliferation, and migration.
- Co-immunoprecipitation and colocalization studies to examine CEACAM1-beta-catenin interactions.
- Analysis of Wnt signaling pathway activity (GSK3-beta, beta-catenin, TCF/LEF, c-Myc, cyclin D1).
Main Results:
- Ceacam1(-/-) intestinal cells showed decreased apoptosis but no changes in proliferation or migration.
- Apc(1638N/+):Ceacam1(-/-) mice exhibited increased intestinal tumor multiplicity and progression.
- CEACAM1-L was found to associate with beta-catenin.
- CEACAM1 deficiency led to decreased GSK3-beta activity, nuclear beta-catenin localization, and enhanced Wnt/TCF/LEF transcriptional activity.
- Upregulation of c-Myc and cyclin D1 was observed in Ceacam1(-/-) intestine.
Conclusions:
- CEACAM1 actively participates in Wnt signaling regulation within intestinal cells.
- Downregulation of CEACAM1 in intestinal tissue contributes to malignancy by increasing tumor multiplicity and progression.
- CEACAM1 loss promotes intestinal tumorigenesis through modulation of apoptosis and Wnt pathway activation.
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