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Carcinoembryonic antigen (CEA) is a tumor marker for the most common forms of adenocarcinomas. We have previously described C57BL/6 mice transgenic for the complete human CEA gene. Compared with humans, these mice reveal a conserved spatiotemporal CEA expression pattern. To establish animal models for CEA-targeted tumor immunotherapy, we have crossed CEA transgenic mice with mice that are genetically predisposed to tumor development. These immunocompetent animals should allow optimization of immunotherapy strategies for maximal destruction of tumor tissues with minimal damage to CEA-expressing normal tissues. To develop a breast tumor model, CEA transgenic mice were cross-bred with mice transgenic for the rat neu protooncogene controlled by the mouse mammary tumor virus long terminal repeat. Female offspring developed poorly differentiated breast tumors, none of which, however, expressed CEA. As a model for colorectal tumors, mice bearing a mutation in the Apc gene (Min mice) and the CEA transgene developed multiple intestinal adenomas with strong CEA expression in all tumor cells. CEA expression had no significant effect on tumor growth. Occasional, well-differentiated breast adenocarcinomas in female offspring expressed CEA focally in tumor cells lining pseudolumina. Cross-breeding Apc(Min/+) mice with neu transgenic mice did not reveal a synergistic effect on the kinetics of breast tumor formation. Finally, CEA transgenic mice crossbred with mice transgenic for the SV40 large T antigen regulated by the surfactant protein-C promoter, developed multiple lung adenocarcinomas that revealed a mosaic CEA expression pattern.

Carcinoembryonic antigen gene family member 2 (CGM2), a member of the carcinoembryonic antigen (CEA) family, is expressed in normal colon and rectum but is down-regulated in colorectal adenocarcinomas. In situ hybridization studies demonstrate that CGM2 expression is limited to epithelial cells in the upper third of the crypts. Two other CEA family members, biliary glycoprotein (BGP) and nonspecific cross-reacting antigen (NCA), are similarly expressed, whereas CEA transcripts were found down to the base of the crypts but were less predominant in the upper region. Only low CGM2 and BGP mRNA levels were seen in colorectal tumors. CEA mRNA was expressed at an equivalent level in normal epithelia and in tumor cells, whereas NCA transcript levels were upregulated in tumor cells. Monoclonal antibodies that recognize the CGM2 protein reveal its presence on the apical membranes of epithelial cells in the upper third of the crypts but its absence from colorectal tumors, which do express the CEA and NCA-50/90 proteins. The newly cloned CGM2 3'-untranslated region was used to probe RNAs from adenomas, colorectal tumors at different stages of progression, and liver metastases of colorectal adenocarcinomas. This showed that CGM2 is already down-regulated in adenomas when compared to normal mucosae. The CGM2 expression pattern along with its sequence homology to BGP suggests a similar tumor suppressor function for CGM2.