Binding properties of monoclonal antibodies recognizing external epitopes of the human MDR1 P-glycoprotein
| Autor: | Frank Baas, Igor B. Roninson, Eugene B. Mechetner, A.H. Schinkel, J. J. M. Smit, Robert J. Arceci, Els Wagenaar, Piet Borst, M. Dolle, Takashi Tsuruo |
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| Přispěvatelé: | Other departments |
| Rok vydání: | 1993 |
| Předmět: |
Cancer Research
Glycosylation medicine.drug_class Molecular Sequence Data Drug Resistance Transfection Monoclonal antibody Epitope Mice Tumor Cells Cultured medicine Animals Humans ATP Binding Cassette Transporter Subfamily B Member 1 Amino Acid Sequence Melanoma Binding selectivity P-glycoprotein chemistry.chemical_classification Membrane Glycoproteins biology Cell Membrane Antibodies Monoclonal Fibroblasts Flow Cytometry Molecular biology Oncology chemistry Cell culture biology.protein Antibody Carrier Proteins Glycoprotein |
| Zdroj: | International journal of cancer. Journal international du cancer, 55(3), 478-484. Wiley-Liss Inc. |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.2910550326 |
| Popis: | Monoclonal antibodies (MAbs) recognizing external epitopes of the human MDRI P-glycoprotein have been used both for the detection of multidrug-resistant cells and as specific inhibitors of P-glycoprotein-mediated multidrug resistance. Using a panel of recently developed transfected or transgenic cell lines containing variants of the human MDRI and MDR3 P-glycoproteins, we have compared the specificity and binding properties of the previously isolated MAbs MRK16, HYB-241, UIC2 and 4E3, and of the newly isolated MAb 7G4. The removal of 1, 2 or all 3 of the N-glycosylation sites present in the first extracellular loop of MDR1 P-glycoprotein did not significantly affect the binding of these MAbs. In contrast, a 20 amino acid deletion in the first extracellular loop of MDR1 P-glycoprotein completely abolished binding of UIC2, whereas the binding of all other MAbs was hardly affected. None of the MAbs tested bound detectably to cell lines containing a high level of the human MDR3 P-glycoprotein. The differences in the binding specificity between UIC2 and the other tested antibodies parallel the reported functional differences in the ability of these antibodies to inhibit P-glycoprotein-mediated drug efflux. |
| Databáze: | OpenAIRE |
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