Characterization of murine carcinoembryonic antigen gene family members

Abstract

Abstract. The carcinoembryonic antigen (CEA) is a human tumor marker whose gene belongs to a family with more than 20 members. This gene family codes for a group of proteins with in vitro cell adhesion properties and for a group of abundantly expressed pregnancy-specific glycoproteins (PSG) with unknown functions. As a basis for in vivo functional studies, we have started to analyze the murine CEA gene family and have identified five new members (Cea-2 to Cea-6). eDNA clones were isolated for Cea-2, Cea-3, and Cea-6. The deduced amino acid sequences of Cea-2 and Cea-6 indicate three IgV-like (N), followed by one IgC-like (A) domain (N1-N2-N3-A). We have also partially characterized the Cea-2 gene and two additional ones, Cea-4 and Cea-5. Cea-2 and Cea-4 are separated by only 16 kb, suggesting a close linkage of murine CEA-related genes, as found for the human CEA gene family. Cea-5 was located to the proximal region of mouse Chromosome (Chr) 7, which is syntenic to part of human Chr 19, containing the human CEA gene family cluster. Cea-2, Cea-3, and a Cea-4-1ike gene are differentially transcribed in the placenta during pregnancy, but not in other organs tested. This expression pattern strongly suggests that they represent counterparts of the human PSG subgroup members, despite the presence of multiple IgV-like domains, a feature not found for human PSGs. The more distantly related Cea-5 seems to be ubiquitously expressed. The putative promoter region of Cea-2 lacks typical TATA-or CAAT-boxes, but contains other conserved motifs that could play a role in the initiation of transcription.

Spatiotemporal expression of pregnancy‐specific glycoprotein gene rnCGM1 in rat placenta

“…Assuming an even distribution of the carbohydrate residues, a carbohydrate chain of M, 3100 would be attached to each of the 16 potential N-glycosylation sites of rnCGMl. Using this same value, the rat and mouse PSGs containing three N domains and 6-8 putative N-glycosylation sites (Chen et al, 1992;Rudert et al, 1992) would have a M, of 68-74 kDa. Therefore, it appears likely that the 75 kDa antigen detected by the anti-N1 domain antiserum (Fig.…”

“…In order to balance the action of LGLs, PSGs could interfere with the recognition of fetal trophoblast cells by maternal natural killer cells. Since an amino acid sequence motif related to the tripeptide sequence ArgGlyAsp (RGD) is present in most PSGs (Khan et al, 1992;Rudert et al, 1992), this could occur by blocking adherence of these cell populations via integrin cell surface receptors, some of which recognize this sequence motif (Hynes, 1992). Indeed, integrins are known to be involved in cellkell interactions like platelet aggregation and cell adhesion between leukocytes and endothelial cells during evasation (Springer, 1990).…”

“…Indeed, PSG-related genes and their transcripts have been identified in the rat (Kodelja et al, 1989;Rebstock et al, 1990;Chen et al, 1992) and more recently in the mouse (Rudert et al, 1992). However, rodent PSGs have a different domain organization and a relatively low sequence conservation compared to their human counterparts.…”

Pregnancy-specific glycoproteins: complex gene families regulating maternal-fetal interactions

“…The CEACAM/PSG ancestral gene is thought to be common to both primates and rodents, but subsequent gene duplications led to considerable diversification of protein structure, expression and function (Kammerer & Zimmermann, 2010, Rudert et al, 1992. The CEACAMs are predominately cell membrane-anchored proteins whereas all PSGs are secreted (Kammerer & Zimmermann, 2010).…”

“…However, CEACAMs and PSGs share several structural features. Both CEACAMs and PSGs are encoded by multigene families and both families of proteins have an amino terminal Ig variable-like domain and a variable number of Ig constant-like domains (Kammerer & Zimmermann, 2010, McLellan et al, 2005a, Rudert et al, 1992. There are twelve human and fifteen mouse CEACAM genes that are widely expressed in normal and cancerous tissues (Hammarstrom, 1999, Kuespert et al, 2006, Zebhauser et al, 2005.…”