BACKGROUND: Renal cell carcinomas (RCC) respond poorly to anthracyclines, Vinca alkaloids, and other agents. P-glycoprotein is overproduced in multidrug-resistant cells and thought to function as an energy-dependent drug efflux pump. The authors thus examined the expression level of P-glycoprotein in RCC and transitional cell carcinomas (TCC). METHODS: P-glycoprotein was detected using immunoblotting with a monoclonal antibody against it, C219. RESULTS: Thirty-three of 38 patients with RCC and 3 of 17 patients with TCC had P-glycoprotein positive tumors. The expression level of P-glycoprotein in most of RCC was lower than that in the normal kidney tissues and that of P-glycoprotein in the TCC was very low. The size of P-glycoprotein in 14 RCC and 3 TCC was 5-10 kilodaltons smaller than in the normal renal tissues. The variation of P-glycoprotein size in the RCC was attributed to differential N-linked glycosylation. P-glycoprotein in a RCC was photolabeled by tritiated azidopine, and the labeling was inhibited by some organic agents. P-glycoprotein distributed on the apical or marginal cell surface of the RCC. CONCLUSIONS: These data show that P-glycoprotein was expressed in many RCC, and its expression level, glycosylation, and distribution were altered. These data also suggest that the P-glycoprotein in RCC had similar drug binding site(s) to that in multidrug-resistant cells.
BACKGROUND:Renal cell carcinomas (RCC) respond poorly to anthracyclines, Vinca alkaloids, and other agents. P-glycoprotein is overproduced in multidrug-resistant cells and thought to function as an energy-dependent drug efflux pump. The authors thus examined the expression level of P-glycoprotein in RCC and transitional cell carcinomas (TCC). METHODS:P-glycoprotein was detected using immunoblotting with a monoclonal antibody against it, C219. RESULTS: Thirty-three of 38 patients with RCC and 3 of 17 patients with TCC had P-glycoprotein positive tumors. The expression level of P-glycoprotein in most of RCC was lower than that in the normal kidney tissues and that of P-glycoprotein in the TCC was very low. The size of P-glycoprotein in 14 RCC and 3 TCC was 5-10 kilodaltons smaller than in the normal renal tissues. The variation of P-glycoprotein size in the RCC was attributed to differential N-linked glycosylation. P-glycoprotein in a RCC was photolabeled by tritiated azidopine, and the labeling was inhibited by some organic agents. P-glycoprotein distributed on the apical or marginal cell surface of the RCC. CONCLUSIONS: These data show that P-glycoprotein was expressed in many RCC, and its expression level, glycosylation, and distribution were altered. These data also suggest that the P-glycoprotein in RCC had similar drug binding site(s) to that in multidrug-resistant cells.