HUMAN CARCINOEMBRYONIC ANTIGEN, AN INTERCELLULAR-ADHESION MOLECULE, BLOCKS FUSION AND DIFFERENTIATION OF RAT MYOBLASTS

Human carcinoembryonic antigen (CEA), a widely used tumor marker, is a member of a family of cell surface glycoproteins that are overexpress ed in many carcinomas. CEA has been shown to function in vitro as a ho motypic intercellular adhesion molecule. This correlation of overprodu ction of an adhesion molecule with neoplastic transformation provoked a test of the effect of CEA on cell differentiation. Using stable CEA transfectants of the rat L6 myoblast cell line as a model system of di fferentiation, we show that fusion into myotubes and, in fact, the ent ire molecular program of differentiation, including creatine phosphoki nase upregulation, myogenin upregulation, and beta-actin downregulatio n are completely abrogated by the ectopic expression of CEA. The block ing of the upregulation of myogenin, a transcriptional regulator respo nsible for the execution of the entire myogenic differentiation progra m, indicates that CEA expression intercepts the process at a very earl y stage. The adhesion function of CEA is essential for this effect sin ce an adhesion-defective N domain deletion mutant of CEA was ineffecti ve in blocking fusion and CEA transfectants treated with adhesion-bloc king peptides fused normally. Furthermore, CEA transfectants maintain their high division potential, whereas control transfectants lose divi sion potential with differentiation similarly to the parental cell lin e. Thus the expression of functional CEA on the surface of cells can b lock terminal differentiation and maintain proliferative potential.