1. ¹McGill Cancer Centre, McGill University, Montreal, Quebec, Canada
2. ²Department of Pathology, McGill University, Montreal, Quebec, Canada
3. ³Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, and University of Toronto, Toronto, Ontario, Canada
4. ⁴Departments of Biochemistry, Medicine and Oncology, McGill University, Montreal, Quebec, Canada

Correspondence: Dr N Beauchemin, McGill Cancer Centre, McGill University, McIntyre Building, Room 711, 3655 Promenade Sir-William-Osler, Montreal, QC, Canada H3G 1Y6. E-mail: Nicole.Beauchemin@mcgill.ca

Received 26 November 2005; Revised 20 February 2006; Accepted 20 February 2006; Published online 17 April 2006.

Abstract

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a glycoprotein that is part of the carcinoembryonic antigen and the immunoglobulin superfamilies. We have shown that it functions as a tumor suppressor and that this function depends upon the presence of the longer CEACAM1 cytoplasmic domain. In this report, we describe the generation of a Ceacam1-/- mouse. The Ceacam1-/- colon exhibits increased in vivo proliferation relative to the wild-type counterpart with a corresponding decreased expression of the p21^Cip1 and p27^Kip1 Cyclin D kinase inhibitors. The colonic villi undergo decreased apoptosis. Out of 35 litters of mice, no spontaneous tumors in any tissues normally expressing CEACAM1 were found over the lifespan of the animals, suggesting that CEACAM1 may not be involved in initiation of tumor development. However, when mice are treated with azoxymethane to induce colonic tumors, we find that Ceacam1-/- mice developed a significantly greater number of tumors than their littermate controls. Moreover, the tumor size was greater in the knockout mice relative to that in the wild-type mice. These results indicate that deletion of CEACAM1 favors progression of colon tumorigenesis.