Biosynthesis of carcinoembryonic antigen (CEA) gene family members expressed in human tumor cell lines: evidence for cleavage of the glycosyl phosphatidyl inositol (GPI) anchor by GPI-PLC and GPI-PLD

Three Carcinoembryonic Antigen (CEA) gene family members: CEA, Non-specific cross-reactive antigen 50/90 (NCA) and biliary glycoprotein (BGP) were expressed in the colon carcinoma cell lines LS174T and HT29. The CEA, NCA50/90 and four alternatively spliced BGP transcripts (BGP a-d) were identified. The molecular weights of the mature glycoproteins were: CEA, 180kD; NCA50/90, 70-100 kD; BGP, 85, 120 and 140 kD. Pulse chase experiments demonstrated that CEA first appears as a 165 kD high mannose precursor which is trimmed to a 160 kD intermediate and finally transformed into the mature 180 kD glycoprotein. The precursor form of NCA had a molecular weight of 50 kD. CEA and NCA50/90, but not BGP, were linked to the cell membrane via glycosyl phosphatidyl inositol and could be released from the intact tumor cells by glycosyl phosphatidyl inositol-specific phospholipase C. CEA on isolated membranes and in cell lysates, but not on intact cells, was also cleaved by fresh human serum or purified glycosyl phosphatidyl inositol-specific phospholipase D.