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Identification of a Novel Tumor-associated M_r 110,000 Gene Product in Human Gastric Carcinoma Cells That Is Immunologically Related to Carcinoembryonic Antigen

Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 [S. S., J. S., J. W. G.], and Second Department of Surgery, Kumamoto University Medical School, Honjo 1-1-1, Kumamoto 860, Japan [M. O.].

A novel gene product which is immunologically related to carcinoembryonic antigen (CEA) and constitutively expressed by six of eight human gastric carcinoma cell lines is described. The antigen was initially identified by the differential binding patterns of four monoclonal antibodies (MAbs) which recognize the putative M_r, 180,000 CEA and/or the M_r 90,000 CEA-related gene product, NCA (normal cross-reacting antigen). Western blot analyses of partially purified membrane fractions prepared from Hs 746T gastric carcinoma cells identified an M_r 110,000 antigen. Northern blot analyses using CEA- and NCA-specific complementary DNA probes did not identify any specific CEA or NCA transcripts in polyadenylate-selected mRNA isolated from the Hs 746T cells. Likewise, a probe designed to hybridize with different CEA-related family members failed to identify a CEA-related message in the Hs 746T cells. Subsequent studies revealed that interferon- (IFN-) treatment substantially increased the level of expression of the M_r 110,000 antigen on the Hs 746T and five other gastric cell types that constitutively expressed the antigen. IFN- treatment also de novo induced the expression of the M_r 110,000 antigen on the surface of GaCa gastric carcinoma cells. A high percentage of Hs 746T (i.e., >85%) and GaCa (approximately 75%) gastric carcinoma cells expressed the M_r 110,000 antigen after IFN- treatment; yet, neither cell type expressed CEA or NCA as measured by the binding of the anti-CEA MAb, COL-1, or B6.2, an anti-NCA MAb. In contrast to CEA and NCA, phosphatidylinositol phospholipase C treatment failed to release the M_r 110,000 antigen from the surface of the Hs 746T or IFN--treated GaCa cells, suggesting that membrane attachment of this novel antigen is not via a glycosyl-phosphatidylinositol anchor. Finally, primers that amplify the 420 base pairs of the immunoglobulin-like domain of CEA and NCA detected an appropriately sized product in untreated as well as IFN--treated GaCa cells using the polymerase chain reaction method. Thus, a potentially novel gene product coding for an M_r 110,000 antigen that is strongly upregulated by IFN- has been identified in human gastric carcinoma cells. Immunologically, the antigen shares reactive epitopes with CEA and its related NCA gene product; however, Northern blot analyses, polymerase chain reaction, and phosphatidylinositol phospholipase C results suggest that the antigen may be, at best, a distant relative of the CEA gene family.

¹ To whom requests for reprints should be addressed, at Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, 9000 Rockville Pike, Building 10, Room 8B07, Bethesda, MD 20892.

Received 5/ 8/91. Accepted 7/31/91.