Differentiation and the multiple drug resistance phenotype in human leukemic cells.
A common feature of mammalian cell lines selected for multiple drug resistance is the overexpression of a high-molecular-weight surface membrane glycoprotein(s). While its amount has been shown to be related to the degree of resistance of such cells, its function in this phenomenon remains obscure. Because there are some biochemical and functional similarities between drug-resistant cells and differentiated cells, we asked if resistance-associated glycoproteins were also associated with cellular differentiation. Using three monoclonal antibodies against antigens known to be associated with differentiation and three monoclonal antibodies that distinguish our multiple drug-resistant human leukemic CEM/VLB100 cells from their drug-sensitive counterparts, we found that the resistant cells were neither altered in their apparent state of differentiation nor were they altered in their ability to respond to a differentiation stimulus with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate. We did find, however, that one antibody that recognizes the resistance-associated glycoprotein, Mr 180,000 glycoprotein (gp180), was only minimally altered in amount bound after treatment with the phorbol ester, but two other resistance-associated glycoproteins, Mr 155,000 glycoprotein (gp155) and, to a lesser extent, Mr 130,000 glycoprotein (gp130), were reduced in expression after this treatment. We suggest that the function of the previously described "marker" glycoprotein associated with multiple drug resistance remains unknown, but that the expression of two other resistance-associated glycoproteins also appears to be related to cellular differentiation or maturation in these cells.
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D004351:Drug Resistance; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000276:immunology / Q000473:pathology*; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D011990:Receptors, Transferrin; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D006023:Glycoproteins; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D013755:Tetradecanoylphorbol Acetate