IMMUNOLOGICAL DETECTION OF MEMBRANE-ASSOCIATED HUMAN LUTEINIZING-HORMONE CORRELATES WITH GENE-EXPRESSION IN CULTURED HUMAN CANCER AND FETALCELLS

We have demonstrated the expression of membrane-associated hCG and its subunits and fragments by cells from 78 human cancer cell lines of di fferent types and origins, indicating that such expression is a common phenotypic characteristic of cultured human malignant cells. Because human (h) LH beta has 80% homology with hCG beta and is coded by one o f the seven genes in the gene cluster located in chromosome 19, it was important to determine whether hLH and its beta-subunit are also expr essed as membrane-associated proteins by cells from human cancer cell lines. Thus, 11 cancer cell lines of different types and origins were adapted to grow in serumless medium, with Nutridoma-HU or SP as serum substitute, and analyzed by flow cytometry using two monoclonal antibo dies directed to different conformational epitopes of intact hLH and a monoclonal antibody reacting with an epitope of hLH beta-free. The ce lls were also analyzed simultaneously for the expression of hCG and it s subunits and fragments. Determination of translatable levels of hLK beta and hCG beta messenger RNAs (mRNAs) was performed in cells from s ome of the cancer cell lines, including the JEG-3 choriocarcinoma cell line, and in cells from a human fetal lung cell line. The analytical flow cytometry studies showed that in addition to the expression of me mbrane-associated hCG in all of its forms, expression of membrane-asso ciated intact (hole) hLH and its free beta-subunit occurred in every c ase. These findings were corroborated by the presence of translatable levels of hLH beta and hCG beta mRNAs in all of the cancer cell lines analyzed, indicating that the expression of these membrane-associated glycoproteins is a phenotypic characteristic of human cancer cells and that the activation of the hCG beta-hLH beta gene cluster is nonselec tive. The presence of translatable levels of hCG beta-hLH beta mRNAs i n the cultured human fetal lung cells punctuates once more the in vivo and in vitro biochemical similarities between fetal and cancer cells.