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Detection of P-glycoprotein in multidrug-resistant cell lines by monoclonal antibodies

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Abstract

One reason for the failure of chemotherapy in the treatment of advanced cancers may be the outgrowth of multidrug-resistant tumour cells1–5. Multidrug resistance has been modelled in numerous mammalian cell lines in which the phenotype is characterized by a pleiotropic cross-resistance to unrelated drugs1–7. In the study reported here, we have produced monoclonal antibodies whose binding to plasma membranes of different multidrug-resistant mammalian cells correlates with the degree of drug resistance. All these antibodies are specific for P-glycoprotein, a cell surface component of relative molecular mass (Mr) 170,000 (170K) that has been described previously8–15, and are directed against three spatially distinct epitopes which define a conserved cytoplasmic domain in the C-terminal region of the P-glycoprotein polypeptide. The conserved nature of P-glycoprotein and its low-level expression in drug-sensitive cells suggest that it has an important function at the cell surface. The monoclonal antibodies against P-glycoprotein described here might serve as diagnostic reagents for clinically unresponsive tumours16.

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References

  1. Ling, V. in Drug Resistance and Neoplasia Vol. 1 (eds Bruchovsky, N. & Goldie, J. H.) 1–19 (CRC Press, Florida, 1982).

    Google Scholar 

  2. Ling, V., Gerlach, J. & Kartner, N. Breast Cancer Res. Treat. 4, 89–94 (1984).

    Article  CAS  Google Scholar 

  3. Curt, G. A., Clendeninn, N. J. & Chabner, B. A. Cancer Treat. Rep. 68, 87–99 (1984).

    CAS  PubMed  Google Scholar 

  4. Riordan, J. R. & Ling, V. in The International Encyclopedia of Pharmacology and Therapeutics (ed. Goldman, I. D.) (Pergamon, New York, in the press).

  5. Biedler, J. L. & Peterson, R. H. F. in Molecular Actions and Targets for Cancer Chemotherapeutic Agents (eds Sartorelli, A. C., Lazo, J. S. & Bertino, J. R.) 453–482 (Academic, New York, 1981).

    Google Scholar 

  6. Kaye, S. & Merry, S. Cancer Chemother. Pharmac. 14, 96–103 (1985).

    Article  CAS  Google Scholar 

  7. Beck, W. T. Adv. Enzyme Regul. 22, 207–227 (1984).

    Article  CAS  Google Scholar 

  8. Juliano, R. L. & Ling, V. Biochim. biophys. Acta 455, 152–162 (1976).

    Article  CAS  Google Scholar 

  9. Juliano, R., Ling, V. & Graves, J. J. supramolec. Struct. 4, 521–526 (1976).

    Article  CAS  Google Scholar 

  10. Riordan, J. R. & Ling, V. J. biol. Chem. 254, 12701–12705 (1979).

    CAS  PubMed  Google Scholar 

  11. Kartner, N., Shales, M., Riordan, J. R. & Ling, V. Cancer Res. 43, 4413–4419 (1983).

    CAS  PubMed  Google Scholar 

  12. Kartner, N., Riordan, J. R. & Ling, V. Science 221, 1285–1288 (1983).

    Article  ADS  CAS  Google Scholar 

  13. Giavazzi, R., Kartner, N. & Hart, I. R. Cancer Chemother. Pharmac. 13, 145–147 (1984).

    Article  CAS  Google Scholar 

  14. Ling, V., Kartner, N., Sudo, T., Siminovitch, L. & Riordan, J. R. Cancer Treat. Rep. 67, 869–874 (1983).

    CAS  PubMed  Google Scholar 

  15. Debenham, P. G., Kartner, N., Siminovitch, L., Riordan, J. R. & Ling, V. Molec. cell. Biol. 2, 881–889 (1982).

    Article  CAS  Google Scholar 

  16. Bell, D. R., Gerlach, J. H., Kartner, N., Buick, R. N. & Ling, V. J. clin. Oncol. 3, 311–315 (1985).

    Article  CAS  Google Scholar 

  17. Riordan, J. R. et al. Nature 316, 817–819 (1985).

    Article  ADS  CAS  Google Scholar 

  18. Westhof, E. et al. Nature 311, 123–126 (1984).

    Article  ADS  CAS  Google Scholar 

  19. Tainer, J. A. et al. Nature 312, 127–134 (1984).

    Article  ADS  CAS  Google Scholar 

  20. Benjamin, D. C. et al. A. Rev. Immun. 2, 67–101 (1984).

    Article  CAS  Google Scholar 

  21. Tsuruo, T. Cancer Chemother. Rep. 67, 889–894 (1983).

    CAS  Google Scholar 

  22. Rogan, A. M., Hamilton, T. C., Young, R. C., Klecker, R. W. & Ozols, R. F. Science 224, 994–996 (1984).

    Article  ADS  CAS  Google Scholar 

  23. Ling, V. & Thompson, L. H. J. cell. Physiol. 83, 103–116 (1974).

    Article  CAS  Google Scholar 

  24. Bech-Hansen, N. T., Till, J. E. & Ling, V. J. cell. Physiol. 88, 23–31 (1979).

    Article  Google Scholar 

  25. Ling, V. Can. J. Genet. Cytol. 17, 503–515 (1975).

    Article  CAS  Google Scholar 

  26. Kuo, T., Pathak, S., Ramagli, L., Rodriguez, L. & Hsu, T. C. in Gene Amplification (ed. Schimke, R. T.) 53–57 (Cold Spring Harbor Laboratory, New York, 1982).

    Google Scholar 

  27. Simard, R. & Cassingena, R. Cancer Res. 29, 1590–1597 (1969).

    CAS  PubMed  Google Scholar 

  28. Langelier, Y., Simard, R. & Brailovsky, C. Differentiation 2, 261–267 (1974).

    Article  CAS  Google Scholar 

  29. Giavazzi, R., Scholar, E. & Hart, I. R. Cancer Res. 43, 2216–2222 (1983).

    CAS  PubMed  Google Scholar 

  30. Siegfried, J. M., Tritton, T. R. & Sartirelli, A. C. Eur. J. Cancer din. Oncol. 19, 1133–1141 (1983).

    Article  CAS  Google Scholar 

  31. Beck, W. T., Mueller, T. J. & Tanzer, L. R. Cancer Res. 39, 2070–2076 (1979).

    CAS  PubMed  Google Scholar 

  32. Peterson, G. L. Analyt. Biochem. 83, 346–356 (1977).

    Article  CAS  Google Scholar 

  33. Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J. J. biol Chem. 193, 265–275 (1951).

    CAS  PubMed  Google Scholar 

  34. Gefter, M. L., Margulies, D. H. & Scharff, M. D. Somat. Cell Genet. 3, 231–235 (1977).

    Article  CAS  Google Scholar 

  35. Shulman, M., Wilden, C. D. & Köhler, G. Nature 276, 269–270 (1978).

    Article  ADS  CAS  Google Scholar 

  36. Towbin, H., Staehelin, T. & Gordon, J. Proc. natn. Acad. Sci. U.S.A. 76, 4350–4354 (1979).

    Article  ADS  CAS  Google Scholar 

  37. Ey, P. L., Prowse, S. J. & Jenkin, C. R. Immunochemistry 15, 429–436 (1978).

    Article  CAS  Google Scholar 

  38. Greenwood, F. C., Hunter, W. M. & Glover, J. S. Biochem. J. 89, 114–123 (1963).

    Article  CAS  Google Scholar 

  39. Davis, F. M., Tsao, T. Y., Meyers, M. B., Peterson, R. H. F. & Spengler, B. A. Cancer Treat. Rep. 67, 859–867 (1983).

    Google Scholar 

  40. Fairbanks, G., Steck, T. L. & Wallach, D. F. H. Biochemistry 10, 2606–2616 (1971).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Ontario Cancer Institute, Princess Margaret Hospital,

    Norbert Kartner, Deanna Evernden-Porelle, Grace Bradley & Victor Ling

  2. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, M4X 1K9

    Norbert Kartner, Deanna Evernden-Porelle, Grace Bradley & Victor Ling

Authors
  1. Norbert Kartner
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  2. Deanna Evernden-Porelle
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  3. Grace Bradley
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  4. Victor Ling
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Kartner, N., Evernden-Porelle, D., Bradley, G. et al. Detection of P-glycoprotein in multidrug-resistant cell lines by monoclonal antibodies. Nature 316, 820–823 (1985). https://doi.org/10.1038/316820a0

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