Molecular characterization of a new gene, CEAL1, encoding for a carcinoembryonic antigen-like protein with a highly conserved domain of eukaryotic translation initiation factors.
Carcinoembryonic antigen (CEA) is a complex immunoreactive glycoprotein belonging to a large and heterogeneous group of cross-reacting proteins known as the CEA gene family, which contains 29 genes/pseudogenes. CEA is used as a valuable serum tumor marker for monitoring response to therapy in patients with various solid tumors. Through the positional cloning approach we have identified and characterized a CEA-like gene (CEAL1), a novel member of the CEA multigene family. We have characterized the complete genomic structure of CEAL1, as well as one alternative splice variant and determined its chromosomal localization. The new gene is comprised of eight exons, with seven intervening introns and it is localized to chromosome 19q13.2 between the markers D19S574 and D19S219, approximately 60 kb upstream of the BCL3 gene. The protein-coding region of the gene is formed of 903 bp, encoding for a 300-amino-acid polypeptide with a predicted molecular weight of 32.6 kDa and isoelectric point of 5.74. The CEAL1 protein contains two Immunoglobulin-like (Ig-like) transmembrane domains, which are present in most of the CEA proteins, as well as one highly conserved domain of eukaryotic translation initiation factors. The identified alternative spliced variant has one more exon of 134 bp. This splice variant is expected to encode for a truncated protein of 142 amino acids with the eIF5A domain and without Ig homology domain. CEAL1 mRNA is expressed in a variety of tissues, but highest levels are found in the prostate, uterus, fetal brain, mammary, adrenal gland, skeletal muscle, small intestine and kidney. CEAL1 is highly expressed in BT-474, BT20, T47D and, at much lower levels, in MCF7 breast cancer cell lines. The new gene is also highly expressed in the LNCaP prostate cancer cell line. The CEAL1 gene was found to be down-regulated by dexamethasone in BT-474 breast cancer cell lines. Our data suggest that this gene is overexpressed in a subset of ovarian cancers which are clinically more aggressive.
Scorilas
Andreas
A
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, M5G 1X5, Toronto, ON, Canada. scorilas@netscape.net
Chiang
Pui Ming
PM
Katsaros
Dionyssios
D
Yousef
George M
GM
Diamandis
Eleftherios P
EP
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D002272:Carcinoembryonic Antigen / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005091:Exons; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005796:Genes / Q000235:genetics; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology; D010448:Peptide Initiation Factors / Q000235:genetics*; D016601:RNA-Binding Proteins; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D000097574:Eukaryotic Translation Initiation Factor 5A
D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D004247:DNA; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C476062:CEACAM19 protein, human