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The multidrug-resistance gene MDR1 is expressed in human glial tumors

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Summary

The most consistantly reported alteration of multidrug-resistant carcinoma cells is the overexpression of a membrane glycoprotein, termed P-glycoprotein. In this study we examined whether the strong intrinsic chemotherapy resistance of glial tumors might be related to the expression of the MDR1 gene which codes for P-glycoprotein. Fourteen glial tumors were examined immunohistochemically using the monoclonal antibody C219. In addition, RNA samples of 11 of these tumors were analysed using a sensitive Northern blot assay. P-glycoprotein is expressed in all 14 glial tumors; the number of stained tumor cells, however, varied considerably ranging from 0.3% to 15%. There was no correlation between the number of MDR1-positive cells and the histological malignancy. Varying amounts of MDR1 mRNA were detectable in 7 from 11 examined tumors. The results of our study show that the MDR1 gene is expressed in human glial tumors and suggest that the multidrug transporter may contribute to the clinical non-responsiveness of these tumors to chemotherapy.

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References

  1. Auffray C, Rougeon F (1980) Purification of mouse immunoglobin heavy chain mRNAs from total myeloma tumor RNA. Eur J Biochem 107:303–314

    Google Scholar 

  2. Biedler JL, Chang T, Meyers MB, et al (1983) Drug resistance in Chinese hamster lung and mouse tumor cells. Cancer Treat Rep 67:859–868

    Google Scholar 

  3. Cordell JL, Falini B, Erber WN, Ghoch AK, Abdulaziz Z, McDonald S, Pulford KA, Stein H, Mason DY (1984) Immunoenzymatic labelling of monoclonal anti-alkaline phosphatase. J Histochem Cytochem 32:219–229

    Google Scholar 

  4. Cordon-Cardo C, O'Brien JP, Casals D, Rittman-Grauer L, Biedler JL, Melamed MR, Bertino JR (1989) Multidrugresistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc Natl Acad Sci USA 86:695–698

    Google Scholar 

  5. Dano K (1973) Active outward transport of daunomycin in resistant Ehrlich ascites tumor cells. Biochim Biophys Acta 323:466–483

    Google Scholar 

  6. Fojo AT, Ueda K, Slamon DJ, et al (1987) Expression of a multidrug-resistance gene in human tumors and tissues. Proc Natl Acad Sci USA 84:265–269

    Google Scholar 

  7. Fuqua SA, Moretti-Rojay IM, Schneider S, McGuire WL (1987) P-glycoprotein expression in human breast cancer cells. Cancer Res 47:2103–2106

    Google Scholar 

  8. Georges E, Bradley G, Gariepy J, Ling V (1990) Detection of P-glycoprotein isoforms by gene-specific monoclonal antibodies. Proc Natl Acad Sci USA 87:152–156

    Google Scholar 

  9. Goldstein LJ, Galski H, Fojo A, Willingham M, Lai SL, Gazdar A, Pirker R, Green A, Crist W, Brodeur G, Lieber M, Cossman J, Gottesman MM, Pastan I (1989) Expression of a multidrug resistance gene in human cancer. J Natl Cancer Inst 81:116–124

    Google Scholar 

  10. Gottesman MM, Pastan I (1988) The multidrug transporter, a double-edged sword. J Biol Chem 263:12163–12166

    Google Scholar 

  11. Greenburger LM, Lothstein L, Williams S, Horwitz S (1988) Distinct P-glycoprotein precursors are overproduced in independently isolated drug-resistant cell lines. Proc Natl Acad Sci USA 85:3762–3766

    Google Scholar 

  12. Gros P, Ben-Neriah Y, Croop J, Housman DE (1986) Isolation and expression of a cDNA (mdr) that confers multidrug resistance. Nature 323:728–731

    Google Scholar 

  13. Juliano RL and Ling V (1976) A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 455:152–162

    Google Scholar 

  14. Kartner N, Evernden-Porelle D, Bradley G, Ling V (1985) Detection of P-glycoprotein in multidrug-resistant cell lines by monoclonal antibodies. Nature 316:820–823

    Google Scholar 

  15. Manz HJ (1974) The pathology of cerebral edema. Hum Pathol 5:291–313

    Google Scholar 

  16. Matsumoto T, Tani E, Kaba K, Kochi N, Shindo H, Yamamoto Y, Sakamoto H, Furuyama J (1990) Amplification and expression of a multidrug resistance gene in human glioma cell lines. J Neurosurg 72:96–101

    Google Scholar 

  17. Riordan JR, Ling V (1979) Purification of P-glycoprotein from plasma membrane vesicles of Chinese hamster ovary cell mutants with reduced colchicine permeability. J Biol Chem 254:12701–12705

    Google Scholar 

  18. Riordan JR, Ling V (1985) Genetic and biochemical characterization of multidrug resistance. Pharmacol Ther 28:51–75

    Google Scholar 

  19. Schluesener HJ, Meyermann R (1990) Spontaneous multidrug transport in human glioma cells is regulated by transforming growth factors type β. Acta Neuropathol (in press)

  20. Sugawara I, Kataoka I, Morishita Y, et al (1987) Tissue distribution of P-glycoprotein encoded by a multidrug-resistant gene as revealed by a monoclonal antibody. MRK16. Cancer Res 48:1926–1929

    Google Scholar 

  21. Thiebault F, Tsuruo T, Hamada H, Gottesman M, Pastan I, Wilingham M (1987) Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissue. Proc Natl Acad Sci USA 84:7735–7738

    Google Scholar 

  22. Thiebault F, Tsuro T, Hamada H, Gottesman MM, Pastan I, Willingham MC (1989) Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein P170: evidence for localization in brain capillaries and cross-reactivity of one antibody with muscle protein. J Histochem Cytochem 37:159–164

    Google Scholar 

  23. Volm M, Bak M, Efferth T, Mattern M (1989) Induced multidrug resistance in murine leukemia L1210 and associated changes in a surface-membrane glycoprotein. Cancer Res Clin Oncol 115:17–24

    Google Scholar 

  24. Walker MD, Alexander E, Hunt W, Maccarty C, Mahaley M, Mealey J, Norrell HA, Owens G, Ransohoff J, Wilson C, Gehan E, Strike TA (1978) Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. J Neurosurg 49:333–343

    Google Scholar 

  25. Weller RO, Foy M, Cox S (1977) The development and ultrastructure of the microvasculature in malignant gliomas. Neuropathol Appl Neurobiol 3:307–322

    Google Scholar 

  26. Willingham MC, Cornwell MM, Cardarelli CO et al (1986) Single cell analysis of daunomycin uptake and efflux in multidrug-resistant and sensitive KB cells: effects of verapamil and other drugs. Cancer Res 46:5941–5946

    Google Scholar 

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Authors and Affiliations

  1. Institut für Hirnforschung der Universität Tübingen, Calwer Strasse 3, W-7400, Tübingen, Federal Republic of Germany

    I. Becker & R. Meyermann

  2. Physiologisches Institut, Pettenkoferstrasse 12, W-8000, München, Federal Republic of Germany

    K. -F. Becker & V. Höllt

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  1. I. Becker
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  2. K. -F. Becker
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  3. R. Meyermann
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  4. V. Höllt
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Becker, I., Becker, K.F., Meyermann, R. et al. The multidrug-resistance gene MDR1 is expressed in human glial tumors. Acta Neuropathol 82, 516–519 (1991). https://doi.org/10.1007/BF00293387

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  • DOI: https://doi.org/10.1007/BF00293387

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