Monoclonal antibody to an external epitope of the human mdr1 P-glycoprotein.
Monoclonal antibody to an external epitope of the human mdr1 P-glycoprotein.
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DOI：
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发表时间：
1993-01
期刊：
影响因子：
11.2
通讯作者：
R. Arceci;K. Stieglitz;J. Brás;A. Schinkel;F. Baas;J. Croop
中科院分区：
文献类型：
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作者：
R. Arceci;K. Stieglitz;J. Brás;A. Schinkel;F. Baas;J. Croop
A membrane glycoprotein, termed P-glycoprotein, has been shown to be responsible for cross-resistance to a broad range of structurally and functionally distinct cytotoxic agents. P-glycoprotein, encoded in humans by the mdr1 gene, functions as an energy-dependent efflux pump to exclude these cytotoxic agents from the resistant cell. In order to study the phenomenon of multidrug resistance in both normal and neoplastic cells, we have generated a mouse monoclonal antibody directed to an external epitope of the human P-glycoprotein. This monoclonal antibody, 4E3, is an IgG2a class antibody which specifically recognizes the human mdr1 P-glycoprotein but not the mdr3 gene product. The 4E3 monoclonal antibody immunoprecipitates both the glycosylated and nonglycosylated forms of P-glycoprotein under mild denaturation conditions. In addition, 4E3 can detect P-glycoprotein in immunocytochemical analysis of fixed tissue-cultured cells and in analysis of frozen sections of human tissue. Binding of the monoclonal antibody to multidrug-resistant cells does not significantly affect the intracellular accumulation or potentiate the cytotoxicity of daunomycin in multidrug-resistant cells. However, at high concentrations of antibody, 4E3 produces a mild potentiation of vinblastine and actinomycin cytotoxicity in multidrug-resistant cells. This monoclonal antibody will be useful both for analyzing P-glycoprotein expression in normal and neoplastic cells and for isolating live cells expressing the P-glycoprotein without significantly affecting the efflux functions of the transporter.
