Carcinoembryonic antigen cell adhesion molecule 1: Cancer and metabolic regulation.

摘要

Carcinoembryonic antigen cell adhesion molecule 1, CEACAM1, is a glycoprotein and a member of the CEA (carcinoembryonic antigen) family of genes. It is expressed on the surface of epithelial, endothelial, and hematopoietic cells, within the gastrointestinal tract, reproductive organs, liver, lungs and kidney. CEACAM1 plays a role in inhibiting the immune response, in cell adhesion, in insulin clearance, in cellular apoptosis and proliferation, in angiogenesis, and functions as a tumor suppressor.;The Ceacam1-/- mouse is also a model for obesity and CEACAM1 is a key factor in insulin clearance. Due to defective insulin clearance, the Ceacam1-/- mice suffer from insulin resistance, and altered lipid synthesis. As these mice age, their weight and abdominal fat increase, and they present signs of hepatic steatosis. In this work, the important roles of CEACAM1 in carcinogenesis and metabolism have been elucidated.;In humans, CEACAM1 is dysregulated and often lower in hyperplastic lesions than in normal tissue, especially in cases of colon, prostate, liver, and 30% of breast cancers. The role of CEACAM1 in tumor formation was studied using the Ceacam1-/- mouse model, which sustained systemic ablation of CEACAM1. In the absence of CEACAM1, epithelial cells from small intestine and colon undergo less apoptosis than in wild-type cells. Moreover, there is increased proliferation in the Ceacam1-/- colonocytes. As CEACAM1 inactivation alone is not sufficient to induce tumors in the mice, the chemical carcinogen, azoxymethane, was used to induce colon tumors. Ceacam1-/- mice developed a higher tumor burden than wild-type mice. One drawback to chemical carcinogenesis is that multiple mutations in unidentified genes cause tumors. To understand the contribution of CEACAM1 to tumor development, the Ceacam1-/- mice was mated with the genetically modified mouse Apc1638N/+ that spontaneously forms small intestinal tumors. Compound Apc 1638N/+: Ceacam1-/- mice developed more tumors than Apc1638N/+ mice, and these tumors progressed to a more advanced stage. In addition, Ceacam1 -/- enterocytes showed compromised Wnt signalling.