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Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines

Nature volume 316, pages 817–819 (1985)Cite this article

Abstract

The multidrug-resistance phenotype expressed in mammalian cell lines is complex. Cells selected with a single agent can acquire cross-resistance to a remarkably wide range of compounds which have no obvious structural or functional similarities1–6. The basis for cross-resistance seems to be a decreased net cellular accumulation of the drugs involved, and has been attributed to alterations in the plasma membrane. An over-expressed plasma membrane glycoprotein of relative molecular mass (Mr) 170,000 (P-glycoprotein) is consistently found in different multidrug-resistant human and animal cell lines, and in transplantable tumours1,2,6–10. Consequently, it has been postulated that P-glycoprotein directly or indirectly mediates multidrug resistance7–11. Here we report the cloning of a complementary DNA encoding P-glycoprotein. Southern blot analysis of hamster, mouse and human DNA using this cDNA as a probe showed that P-glycoprotein is conserved and is probably encoded by a gene family, and that members of this putative family are amplified in multidrug-resistant cells.

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Authors and Affiliations

  1. Research Institute, Hospital for Sick Children,

    John R. Riordan & Noa Alon

  2. Departments of Biochemistry and Clinical Biochemistry, University of Toronto, Toronto, Ontario, Canada, M5G 1X8

    John R. Riordan & Noa Alon

  3. Ontario Cancer Institute, Princess Margaret Hospital and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, M4X 1K9

    Kathryn Deuchars, Norbert Kartner & Victor Ling

  4. Department of Internal Medicine and the Cancer Center, University of Arizona, Tucson, Arizona, 85724, USA

    Jeffrey Trent

Authors
  1. John R. Riordan
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  2. Kathryn Deuchars
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  3. Norbert Kartner
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  4. Noa Alon
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  5. Jeffrey Trent
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  6. Victor Ling
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Riordan, J., Deuchars, K., Kartner, N. et al. Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines. Nature 316, 817–819 (1985). https://doi.org/10.1038/316817a0

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