Deletion of the carcinoembryonic antigen-related cell adhesion molecule 1 (Ceacam1) gene contributes to colon tumor progression in a murine model of carcinogenesis
Deletion of the carcinoembryonic antigen-related cell adhesion molecule 1 (Ceacam1) gene contributes to colon tumor progression in a murine model of carcinogenesis
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DOI：
10.1038/sj.onc.1209541
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发表时间：
2006-09-01
期刊：
影响因子：
8
通讯作者：
Beauchemin, N.
中科院分区：
文献类型：
--
作者：
Leung, N.;Turbide, C.;Beauchemin, N.
癌胚抗原相关细胞粘附分子1 （CEACAM1）是一种糖蛋白，是癌胚抗原和免疫球蛋白超家族的一部分。我们已经证明它作为肿瘤抑制因子起作用，并且这种功能依赖于较长的CEACAM1细胞质结构域的存在。在本报告中，我们描述了Ceacam1-/-小鼠的生成。与野生型相比，Ceacam1-/-结肠在体内增殖增加，相应的p21（Cip1）和p27（Kip1）细胞周期蛋白D激酶抑制剂的表达减少。结肠绒毛细胞凋亡减少。在35窝小鼠中，没有在正常表达CEACAM1的组织中发现自发肿瘤，这表明CEACAM1可能不参与肿瘤发展的起始。然而，当小鼠用偶氮甲烷诱导结肠肿瘤时，我们发现Ceacam1-/-小鼠的肿瘤数量明显高于对照组。此外，与野生型小鼠相比，基因敲除小鼠的肿瘤大小更大。这些结果表明CEACAM1的缺失有利于结肠肿瘤发生的进展。
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.