Deletion of the carcinoembryonic antigen-related cell adhesion molecule 1 (Ceacam1) gene contributes to colon tumor progression in a murine model of carcinogenesis

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 Ceacam1À/À mouse. The Ceacam1À/À colon exhibits increased in vivo proliferation relative to the wild-type counterpart with a corresponding decreased expression of the p21Cip1 and p27Kip1 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 Ceacam1À/À 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.

CEACAM1 impedes thyroid cancer growth but promotes invasiveness: a putative mechanism for early metastases

“…The results showed that CEACAM1 significantly enhanced p21 but not p27 expression and conversely downregulation of CEA-CAM1 decreased p21 but not p27 expression. These data are in partial agreement with a recent report where CEACAM1 depletion was shown to be associated with diminished p21 and p27 in mouse colonic epithelium (Leung et al, 2006).…”

CEACAM1 negatively regulates platelet-collagen interactions and thrombus growth in vitro and in vivo

“…18 Wild-type and ceacam1 ϩ/Ϫ mice were age-and sex-matched C57BL/6. These mice were housed in the Burnet Institute …”

“…18 Antirabbit fluorescein isothiocyanate (FITC) was purchased from Dako (Botany, Australia). Anti-mouse GPVI, 19 anti-mouse GPIb␣/IX/V complex, 20 anti-mouse integrin ␣2␤1, 21 anti-mouse CD9, 22 and anti-mouse GPVI (JAQ1) 23 were purchased or obtained from Emfret Analytics (Wü rzburg, Germany).…”

Intestinal tumor progression is promoted by decreased apoptosis and dysregulated Wnt signaling in Ceacam1−/− mice

“…In support of the role of CEACAM1-L in inhibition of tumor growth, we have recently shown that Ceacam1 À/À normal colon exhibits increased proliferation and decreased apoptosis. Upon azoxymethane carcinogenic induction, a greater number of colon tumors form in CEACAM1-deficient mice relative to littermate controls (Leung et al, 2006). However, as both Ceacam1 and Apc loss of function represent early events in intestinal cancer development, we questioned whether deletion of the Ceacam1 gene influenced intestinal tumor progression driven by the Apc loss of function and whether both genes impacted on the same signaling pathways.…”