Radical differences in functions of closely related members of the human carcinoembryonic antigen gene family.
The immunoglobulin superfamily represents an ancient, highly diversified group of cell surface and extracellular molecules responsible for a wide range of molecular and cellular recognition functions. The human carcinoembryonic antigen (CEA) subfamily of the immunoglobulin superfamily presents evidence of continuing diversification of the immunoglobulin family, in that some of its members, including CEA itself and nonspecific cross-reacting antigen (NCA), are expressed only in primates and not in rodents. These "new" members are glycophosphatidylinositol linked to the external cell membrane and are up-regulated in cancer, unlike members present in both rodents and primates, i.e., biliary glycoprotein (BGP), which are transmembrane linked and down-regulated in cancer. CEA, NCA, and BGP have all been shown to function in vitro as intercellular adhesion molecules. We show here that the properties of adhesion are radically different, in that BGP-mediated adhesion is reversibly Ca2+ and Mg2+ dependent, temperature dependent, and ATP inhibitable, whereas CEA- and NCA-mediated adhesion is the opposite in all aspects. Also, the novel double-reciprocal, antiparallel binding observed for CEA-CEA interactions is not seen for BGP. Finally, the myogenic differentiation block demonstrated for the ectopic expression of CEA in myoblasts was also observed for NCA but not for BGP, which is consistent with the changes in expression seen in cancer. The appearance of new CEA family members with such different properties is discussed in the context of evolution and cancer.
Rojas
M
M
McGill Cancer Centre, McGill University, Montreal, Quebec, Canada.
DeMarte
L
L
Screaton
R A
RA
Stanners
C P
CP
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm / Q000502:physiology; D016466:CHO Cells / Q000166:cytology / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D002272:Carcinoembryonic Antigen / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D008274:Magnesium / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics*; D011485:Protein Binding / Q000502:physiology
D015703:Antigens, CD; D000951:Antigens, Neoplasm; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D000255:Adenosine Triphosphate; D008274:Magnesium; D002118:Calcium