K. Nishiyama et al., EXPRESSION OF THE MULTIDRUG TRANSPORTER, P-GLYCOPROTEIN, IN RENAL ANDTRANSITIONAL-CELL CARCINOMAS, Cancer, 71(11), 1993, pp. 3611-3619
Background. Renal cell carcinomas (RCC) respond poorly to anthracyclin
es, Vinca alkaloids, and other agents. P-glycoprotein is overproduced
in multidrug-resistant cells and thought to function as an energy-depe
ndent drug efflux pump. The authors thus examined the expression level
of P-glycoprotein in RCC and transitional cell carcinomas (TCC). Meth
ods. P-glycoprotein was detected using immunoblotting with a monoclona
l 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 TC
C was very low. The size of P-glycoprotein in 14 RCC and 3 TCC was 5-1
0 kilodaltons smaller than in the normal renal tissues. The variation
of P-glycoprotein size in the RCC was attributed to differential N-lin
ked glycosylation. P-glycoprotein in a RCC was photolabeled by tritiat
ed azidopine, and the labeling was inhibited by some organic agents. P
-glycoprotein distributed on the apical or marginal cell surface of th
e 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.