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Molecular Hepatology Laboratory and Cancer Center, Massachusetts General Hospital and Department of Medicine, Harvard Medical School [M. O., P. M., H. T., L. H., B. B., J. R. W.]; and Harvard-MIT Division of Health Science [M. F., B. W.], Boston, Massachusetts 02114
A Mr 50,000 cell surface protein antigen (p50) was identified on a human hepatocellular carcinoma derived cell line (FOCUS) by two monoclonal antibodies (SF 31 and SF 90). This antigen was subsequently shown to be expressed in vivo in human hepatocellular carcinoma. All 18 tumors tested by Western immunoblotting demonstrated high levels of p50 with undetectable amounts observed in the adjacent normal liver counterparts. Further characterization revealed that p50 is a monomeric polypeptide with a neutral pI (6.57.2) and appears not to be glycosylated. The cellular localization was determined by direct antibody binding to intact cells, immunoprecipitation of 125I-labeled cell surface proteins, and Western immunoblotting of subcellular fractions. p50 was found on the cell surface as well as in the cytoplasm. In vitro monoclonal antibody binding studies indicate that the protein is expressed in all human malignant cells (n = 34) tested thus far regardless of the embryonic tissue of origin and the degree of differentiation. p50 was present at very low levels in normal tissues with the notable exception of high expression in adrenal glands. The protein is conserved in mammalian evolution since a similar protein was also found in bovine adrenals. The molecular characteristics and the pattern of expression of p50 indicate that this normal adrenal protein is associated with the transformed phenotype.
1 This work was supported in part by Grants CA-35711, AA-02666, and HD-20469 from NIH and a grant from Association pour la Recherche sur le Cancer.
2 To whom requests for reprints should be addressed, at Molecular Hepatology Laboratory and Cancer Center, Massachusetts General Hospital, 149 13th Street, 7th Floor, Charlestown, MA 02129.
3 Recipient of a fellowship from Association pour la Recherche sur le Cancer, Villejuif (France) and from the NCI-INSERM Bilateral Program.
4 Recipient of a Research Career Scientist Development Award AA-00048.
Received 4/13/89. Revised 7/13/89. Accepted 8/24/89.
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