Molecular cloning and characterization of the complementary DNA of an M(r) 110,000 antigen expressed by human gastric carcinoma cells and upregulated by gamma-interferon.
An M(r) 110,000 antigen was initially described in human gastric carcinoma cells by its cross-reactivity with anti-carcinoembryonic antigen (CEA) monoclonal antibodies, as well as the ability of gamma-interferon to increase its level of expression. We describe the molecular cloning and sequence analyses of overlapping clones that constitute a full-length complementary DNA that encodes for the entire M(r) 110,000 molecule. The 1.5-kilobase message encodes for a 407-amino acid polypeptide whose structural analysis was consistent with an integral membrane glycoprotein. In particular, the extracellular domain was rich in serine and threonine residues at which carbohydrate substitution is likely through O- and N-linked glycosylation. This would explain the higher molecular weight of the antigen whose polypeptide backbone is approximately M(r) 42,000. Further computer-aided sequence analyses revealed no significant homology with any member of the CEA gene family. The cross-reactivity with anti-CEA monoclonal antibodies may be explained by the presence of CEA and normal cross-reacting antigen homologous sites proximal to the transmembrane region. No sequence homology was found with any known protein. Thus, the M(r) 110,000 molecule represents a potentially novel cell membrane glycoprotein whose possible role in human cancer and/or as a gamma-interferon-inducible gene product warrants further investigation.
Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
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S
Shimada
M
M
Ogawa
M
M
Takahashi
J
J
Schlom
J W
JW
Greiner
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics*; D000953:Antigens, Protozoan / Q000235:genetics; D001483:Base Sequence; D002272:Carcinoembryonic Antigen / Q000235:genetics; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D012333:RNA, Messenger / Q000032:analysis; D012689:Sequence Homology, Nucleic Acid; D013274:Stomach Neoplasms / Q000276:immunology*; D015854:Up-Regulation
D000951:Antigens, Neoplasm; D000953:Antigens, Protozoan; D002272:Carcinoembryonic Antigen; D018076:DNA, Complementary; C063362:QF116 antigen, Plasmodium falciparum; D012333:RNA, Messenger; D007371:Interferon-gamma