Effects of Monensin and Tunicamycin on Cell Surface Expression of Carcinoembrionic Antigen in a Human Gastric Cancer Cell Line

抄録

Carcinoembrionic antigen (CEA) is a glycosyl-phosphatidylinositol (GPI) anchored protein which has N-glycosylation sites. To determine whether it acts as a cell surface adhesion molecule or functions as molecular transportation, we studied the stability and regulation of CEA expression in a human gastric cancer cell line (HPE-GAC-T) using immunological techniques. Amounts of CEA in the cytoplasm of GAC-T cells were increased by stimulation with 12-O-tetra-decanoylphorbol-13-acetate (TPA), with or without calcium ionophore A23187. Synergistic effects of TPA with A23187 (TPA/A23187) on the cell surface expression of CEA were observed dose- and time-dependently. Tunicamycin, an inhibitor of N-linked glycosylation, decreased the total cellular CEA level of mature form of 170kD. Monensin, an inhibitor of intracellular transport, also decreased the amount of high molecular weight (170, 000) CEA, but the smaller molecular weight (140, 000) CEA that appeared by TPA/A23187 treatment remained unaffected. Both drugs suppressed GAC-T cell growth moderately at high doses used, but did not suppress the increased cell surface expression of CEA induced with TPA/A23187. Up-regulation and stability of the membrane expression of CEA may involve the physiological role CEA plays on the cell surface.