Molecular cloning of the CA125 ovarian cancer antigen: identification as a new mucin, MUC16.
CA125 is an ovarian cancer antigen that is the basis for a widely used serum assay for the monitoring of patients with ovarian cancer; however, detailed information on its biochemical and molecular nature is lacking. We now report the isolation of a long, but partial, cDNA that corresponds to the CA125 antigen. A rabbit polyclonal antibody produced to purified CA125 antigen was used to screen a lambdaZAP cDNA library from OVCAR-3 cells in Escherichia coli. The longest insert from the 54 positive isolated clones had a 5797-base pair sequence containing a stop codon and a poly(A) sequence but no clear 5' initiation sequence. The deduced amino acid sequence has many of the attributes of a mucin molecule and was designated CA125/MUC16 (gene MUC16). These features include a high serine, threonine, and proline content in an N-terminal region of nine partially conserved tandem repeats (156 amino acids each) and a C-terminal region non-tandem repeat sequence containing a possible transmembrane region and a potential tyrosine phosphorylation site. Northern blotting showed that the level of MUC16 mRNA correlated with the expression of CA125 in a panel of cell lines. The molecular cloning of the CA125 antigen will lead to a better understanding of its role in ovarian cancer.
Yin
B W
BW
Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Lloyd
K O
KO
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D018394:CA-125 Antigen / Q000235:genetics*; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D009077:Mucins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D018394:CA-125 Antigen; D018076:DNA, Complementary; D009077:Mucins