More than 15 years of CA 125: what is known about the antigen, its structure and its function.
In 1997 CA 125 celebrated its 15th anniversary. Since the discovery of OC 125, an antibody that recognizes CA 125, by Bob Bast and his colleagues, considerable progress has been made toward the development of more sensitive and more precise assay systems. However, a great deal of mystery still remains about the CA 125 molecule and further enlightenment will probably not come until the gene for CA 125 is cloned and the complete open reading frame for the peptide core identified. In the meantime, we have learned some structural features of the CA 125 molecule as well as a little about its regulation and the requirements for its secretion or release from epithelial derived cells in cultures. The CA 125 molecule is almost certainly a glycoprotein with a predominance of O-linkages. It is heterogeneous with regard to both size and charge, most likely due to continuous deglycosylation of side chains during its life-span in bodily fluids. It exists as a very large complex (perhaps as much as 4 million daltons) under natural conditions. The core CA 125 subunit is in excess of 200,000 daltons and it retains the capacity to bind both OC 125 class antibodies and M 11 class antibodies. As a denatured purified subspecies the CA 125 molecule appears to autoproteolyse presumably due to an endogenous protease activity inherent to the molecule. Release or secretion of CA 125 appears directly linked to the epithelial growth factor receptor signal transduction pathway. Prior to its release from cultured cells, CA 125 is phosphorylated (at either/both serine and threonine) and dephosphorylated when released. To stimulate discussion on the regulation of CA 125 synthesis, its secretion and its structural configuration, we have presented a model of a theoretical CA 125 molecule. Perhaps it will provide a focus of attention until the CA 125 gene is cloned and the real molecule is described.
O'Brien
T J
TJ
Department of Obstetrics and Gynecology, Kyoto University, Japan.
Tanimoto
H
H
Konishi
I
I
Gee
M
M
D000906:Antibodies; D001201:Ascites; D018394:CA-125 Antigen / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D003001:Cloning, Molecular; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D006801:Humans; D007118:Immunoassay; D010051:Ovarian Neoplasms / Q000175:diagnosis; D011247:Pregnancy; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000032:analysis / Q000737:chemistry; D012680:Sensitivity and Specificity
D000906:Antibodies; D018394:CA-125 Antigen; D011994:Recombinant Proteins