Expression of the multidrug transporter, P-glycoprotein, in renal and transitional cell carcinomas

K. Nishiyama, T. Shirahama, Akihiko Yoshimura, T. Sumizawa, T. Furukawa, M. Ichikawa- Haraguchi, S. I. Akiyama, Y. Ohi

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Abstract

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.

Original languageEnglish
Pages (from-to)3611-3619
Number of pages9
JournalCancer
Volume71
Issue number11
DOIs
Publication statusPublished - 1993
Externally publishedYes

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Keywords

  • N- linked glycosylation
  • P-glycoprotein
  • renal cell carcinoma
  • transitional cell carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nishiyama, K., Shirahama, T., Yoshimura, A., Sumizawa, T., Furukawa, T., Ichikawa- Haraguchi, M., Akiyama, S. I., & Ohi, Y. (1993). Expression of the multidrug transporter, P-glycoprotein, in renal and transitional cell carcinomas. Cancer, 71(11), 3611-3619. https://doi.org/10.1002/1097-0142(19930601)71:11<3611::AID-CNCR2820711124>3.0.CO;2-T