OPPOSITE FUNCTIONS FOR 2 CLASSES OF GENES OF THE HUMAN CARCINOEMBRYONIC ANTIGEN FAMILY

The human carcinoembryonic antigen (CEA) family can be divided into tw o subgroups according to the means of anchorage of member glycoprotein s to the cell membrane: glycophosphatidyl inositol (GPI) linkage and t ransmembrane linkage. The GPI-linked members tend to be up-regulated i n human tumours, whereas the transmembrane-linked members tend to be d own-regulated. Thus the question as to whether the GPI members could b e formally considered to function as oncogenes and the transmembrane m embers as tumour suppressors deserves consideration. Members of both s ubgroups function in vitro as intercellular adhesion molecules, but th e characteristics of this adhesion, including temperature and divalent -cation dependence, differ markedly between the groups. Even the mecha nism of intermolecular adhesion appears to differ fundamentally in tha t GPI-linked CEA-CEA binding involves a double reciprocal bonding betw een two domains, whereas transmembrane-linked biliary glycoprotein (BG P)BGP binding requires only one domain. Finally, the ectopic expressio n of CEA in myoblasts can block myogenic differentiation leaving the c ells with the ability to divide, while expression of BGP does not affe ct or may even accelerate myogenic differentiation. These differences in phenotypic effects in vitro thus mirror the differences observed in expression in tumours and support the view that the GPI and transmemb rane groups have opposite effects on cells in relation to the malignan t phenotype.