Expression of the multidrug transporter, P-glycoprotein, in renal and transitional cell carcinomas.
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.
Nishiyama
K
K
Department of Cancer Chemotherapy, Faculty of Medicine, Kagoshima University, Japan.
Shirahama
T
T
Yoshimura
A
A
Sumizawa
T
T
Furukawa
T
T
Ichikawa-Haraguchi
M
M
Akiyama
S
S
Ohi
Y
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000345:Affinity Labels; D001386:Azides / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000737:chemistry*; D002295:Carcinoma, Transitional Cell / Q000737:chemistry; D002352:Carrier Proteins / Q000032:analysis*; D004095:Dihydropyridines / Q000378:metabolism; D004351:Drug Resistance; D006801:Humans; D015151:Immunoblotting; D007668:Kidney / Q000737:chemistry*; D007680:Kidney Neoplasms / Q000737:chemistry*; D008562:Membrane Glycoproteins / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000345:Affinity Labels; D001386:Azides; D002352:Carrier Proteins; D004095:Dihydropyridines; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C041130:azidopine