Cloning of the Complete Gene for Carcinoembryonic Antigen

Carcinoembryonic antigen (CEA) is a widely used tumor marker,
especially in the surveillance of colonic cancer patients. Although
CEA is also present in some normal tissues, it is apparently
expressed at higher levels in tumorous tissues than in
corresponding normal tissues. As a first step toward analyzing the
regulation of expression of CEA at the transcriptional level, we
have isolated and characterized a cosmid clone (cosCEA1), which
contains the entire coding region of the CEA gene. A close
correlation exists between the exon and deduced immunoglobulin-like
domain borders. We have determined a cluster of transcriptional
starts for CEA and the closely related nonspecific cross-reacting
antigen (NCA) gene and have sequenced their putative promoters.
Regions of sequence homology are found as far as approximately 500
nucleotides upstream from the translational starts of these genes,
but farther upstream they diverge completely. In both cases we were
unable to find classic TATA or CAAT boxes at their expected
positions. To characterize the CEA and NCA promoters, we carried
out transient transfection assays with promoter-indicator gene
constructs in the CEA-producing adenocarcinoma cell line SW403, as
well as in nonproducing HeLa cells. A CEA gene promoter construct,
containing approximately 400 nucleotides upstream from the
translational start, showed nine times higher activity in the SW403
than in the HeLa cell line. This indicates that cis-acting
sequences which convey cell type-specific expression of the CEA
gene are contained within this region.