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. 1986 Jun;83(11):3847–3850. doi: 10.1073/pnas.83.11.3847

Membrane vesicles from multidrug-resistant human cancer cells contain a specific 150- to 170-kDa protein detected by photoaffinity labeling.

M M Cornwell, A R Safa, R L Felsted, M M Gottesman, I Pastan
PMCID: PMC323621  PMID: 3459160

Abstract

Multiple drug resistance of tumor cells is a common problem in cancer therapy. We have demonstrated that membrane vesicles from highly multidrug-resistant human KB carcinoma cell lines exhibit increased specific and saturable binding of vinblastine. To identify the molecules that bind vinblastine, membrane vesicles from multidrug-resistant cells were exposed to two analogs of vinblastine, N-(p-azido-[3,5-3H]benzoyl)-N'-(beta-aminoethyl)vindesine and N-(p-azido-[3-125I]salicyl)-N'-(beta-aminoethyl)vindesine, that could be photoactivated. Our studies show the specific labeling of a 150- to 170-kDa protein in membrane vesicles from two independently selected multidrug-resistant KB cell lines, which was not seen in drug-sensitive parental or revertant cell lines. The labeling of the high molecular weight protein was inhibited in a dose-dependent manner by vinblastine with half-maximal inhibition at about 1 microM. Photolabeling was also inhibited by 100 microM vincristine or 100 microM verapamil but not by 100 microM colchicine or 100 microM dexamethasone. The data suggest that the 150- to 170-kDa protein may play an important role in the multidrug-resistance phenotype.

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Selected References

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