Detection of P-glycoprotein in multidrug-resistant cell lines by monoclonal antibodies.
One reason for the failure of chemotherapy in the treatment of advanced cancers may be the outgrowth of multidrug-resistant tumour cells. Multidrug resistance has been modelled in numerous mammalian cell lines in which the phenotype is characterized by a pleiotropic cross-resistance to unrelated drugs. In the study reported here, we have produced monoclonal antibodies whose binding to plasma membranes of different multidrug-resistant mammalian cells correlates with the degree of drug resistance. All these antibodies are specific for P-glycoprotein, a cell surface component of relative molecular mass (Mr) 170,000 (170K) that has been described previously, and are directed against three spatially distinct epitopes which define a conserved cytoplasmic domain in the C-terminal region of the P-glycoprotein polypeptide. The conserved nature of P-glycoprotein and its low-level expression is drug-sensitive cells suggest that it has an important function at the cell surface. The monoclonal antibodies against P-glycoprotein described here might serve as diagnostic reagents for clinically unresponsive tumours.
N
N
Kartner
D
D
Evernden-Porelle
G
G
Bradley
V
V
Ling
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004351:Drug Resistance; D000939:Epitopes / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000032:analysis* / Q000276:immunology; D006801:Humans; D008647:Mesocricetus; D051379:Mice; D010053:Ovary; D013045:Species Specificity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D000939:Epitopes; D006023:Glycoproteins