Effects of differentiating agents on cell surface expression of the breast carcinoma-associated DF3-P epitope.
The DF3 antigen is a member of a family of high-molecular-weight glycoproteins aberrantly expressed in human breast carcinomas. Recent work has described the generation of a monoclonal antibody (MAb), designated DF3-P, that reacts with immature, underglycosylated precursors of DF3 antigen. Immunoperoxidase staining studies have demonstrated that MAb DF3-P exhibits selective reactivity with malignant mammary epithelium. Using flow cytometry and live cell radioimmunoassays, the present studies demonstrate that the epitope recognized by MAb DF3-P is expressed on the surface of MCF-7 and other human breast carcinoma cell lines. We also demonstrate that treatment of MCF-7 cells with 12-O-tetradecanoylphorbol-13-acetate, an agent known to induce a more differentiated mammary cell phenotype, is associated with increased expression of the DF3-P epitope. Similar findings were obtained with sodium butyrate. The results indicate that these agents increase both cell surface DF3-P antigen density and the percentage of DF3-P-positive cells. Immunofluorescence studies performed on chamber slides further demonstrate that MAb DF3-P-reactive cells are detectable in small clones or clusters. Similar studies with 12-O-tetradecanoylphorbol-13-acetate- and butyrate-treated cells demonstrate increases in the size and number of these clusters. Taken together, these results indicate that the DF3-P epitope is expressed on the surface of human breast carcinoma cell lines and that the heterogeneity of this expression is related to the presence of differentiating signals.
Perey
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Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Hayes
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DF
Kufe
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D000951:Antigens, Neoplasm / Q000276:immunology / Q000502:physiology*; D001943:Breast Neoplasms / Q000276:immunology*; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002454:Cell Differentiation / Q000187:drug effects; D000939:Epitopes / Q000032:analysis*; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D010641:Phenotype; D011863:Radioimmunoassay; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000951:Antigens, Neoplasm; D002087:Butyrates; D000939:Epitopes; D020148:Butyric Acid; D013755:Tetradecanoylphorbol Acetate