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 overexpressed in many carcinomas. CEA has been shown to function in vitro as a homotypic intercellular adhesion molecule. This correlation of overproduction 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 differentiation, we show that fusion into myotubes and, in fact, the entire molecular program of differentiation, including creatine phosphokinase upregulation, myogenin upregulation, and beta-actin downregulation are completely abrogated by the ectopic expression of CEA. The blocking of the upregulation of myogenin, a transcriptional regulator responsible for the execution of the entire myogenic differentiation program, indicates that CEA expression intercepts the process at a very early stage. The adhesion function of CEA is essential for this effect since an adhesion-defective N domain deletion mutant of CEA was ineffective in blocking fusion and CEA transfectants treated with adhesion-blocking peptides fused normally. Furthermore, CEA transfectants maintain their high division potential, whereas control transfectants lose division potential with differentiation similarly to the parental cell line. Thus the expression of functional CEA on the surface of cells can block terminal differentiation and maintain proliferative potential.
Eidelman
F J
FJ
McGill Cancer Centre, Biochemistry Department, McGill University, Montreal, Quebec, Canada.
Fuks
A
A
DeMarte
L
L
Taheri
M
M
Stanners
C P
CP
D000199:Actins / Q000032:analysis / Q000235:genetics / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002272:Carcinoembryonic Antigen / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002459:Cell Fusion / Q000502:physiology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D003402:Creatine Kinase / Q000032:analysis / Q000235:genetics / Q000502:physiology; D004247:DNA / Q000235:genetics; D015536:Down-Regulation; D008954:Models, Biological; D008969:Molecular Sequence Data; D009132:Muscles / Q000737:chemistry / Q000166:cytology* / Q000196:embryology*; D018008:Myogenin / Q000032:analysis / Q000235:genetics / Q000502:physiology; D051381:Rats; D014162:Transfection; D015854:Up-Regulation
D000199:Actins; D002272:Carcinoembryonic Antigen; C503803:Myog protein, rat; D018008:Myogenin; D004247:DNA; D003402:Creatine Kinase