Abstract
The gene encoding the human tumor marker carcinoembryonic antigen (CEA) belongs to a gene family which can be subdivided into the CEA and the pregnancy-specific glycoprotein subgroups. The corresponding proteins are members of the immunoglobulin superfamily, characterized through the presence of one IgV-like domain and a varying number of IgC-like domains. Since the function of the CEA family is not well understood, we decided to establish an animal model in the rat to study its tissue-specific and developmental stage-dependent expression. To this end, we have screened an 18-day rat placenta cDNA library with a recently isolated fragment of a rat CEA-related gene. Two overlapping clones containing the complete coding region for a putative 709 amino acid protein (rnCGM1; Mr = 78,310) have been characterized. In contrast to all members of the human CEA family, this rat CEA-related protein consists of five IgV-like domains and only one IgC-like domain. This novel structure, which has been confirmed at the genomic level might have important functional implications. Due to the rapid evolutionary divergence of the rat and human CEA gene families it is not possible to assign rnCGM1 to its human counterpart. However, the predominant expression of the rnCGM1 gene in the placenta suggests that it could be analogous to one of the human pregnancy-specific glycoprotein genes.
Highlights
The gene encoding the human tumor marker carcinoembryonic antigen (CEA) belongs to a gene family which can be subdivided into the CEA and the pregnancy-specific glycoprotein subgroups
Isolation and Analysis of Rat CEA-related cDNA ClonesSince we had previously shown that members of the rat CEA gene family are strongly expressed in placenta (Kodelja et al, 1989), we screened a cDNA library which had been constructed from RNA of an 18-day rat placenta
In contrast to all human CEA-like proteins, which are composed of only one Ig variable (IgV)-like or N-terminal domain and a varying number (2, 3, 6) of Ig constant (IgC)-like or half-repeat domains (Thompson et al, 1989a), the rnCGM1 protein contains five IgV-like domains (N,N,), separated by truncated leader-like sequences (L;-LA) of variable length, and only one IgC-like or half-repeat domain (Figs. 1 and 3)
Summary
The gene encoding the human tumor marker carcinoembryonic antigen (CEA) belongs to a gene family which can be subdivided into the CEA and the pregnancy-specific glycoprotein subgroups. Since the function of the CEA family is not well understood, we decided to establish an animal model in the rat to study its tissue-specific and developmental stage-dependent expression. To this end, we have screened an 18-day rat placenta cDNA library with a recently isolated fragment of a rat CEA-related gene. In contrast to all members of the human CEA family, this rat CEA-related protein consists of five IgV-like domains and only one IgC-like domain. This novel structure, which has been confirmed at the genomic level might have important functional implications. Rising CEA serum concentrations are widely used as an indicator of tumor recurrencies during the postoperative surveillance, especially of patients with colorectal carcinomas (Shively and Beatty, 1985)
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