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Isolation and expression of a complementary DNA that confers multidrug resistance

Nature volume 323, pages 728–731 (1986)Cite this article

Abstract

The emergence and outgrowth of a population of tumour cells resistant to multiple drugs is a major problem in the chemotherapeutic treatment of cancer. We have used highly drug-resistant cell lines developed in vitro to study the molecular basis of multidrug resistance. In these cell lines high levels of resistance are frequently associated with amplification and overexpression of a small group of genes termed mdr (refs 1–3) or gp170 (ref. 4). Direct evaluation of the role of these genes in multidrug resistance has awaited the isolation of a member of this gene family in a biologically active form. Here we report the isolation of DNA clones complementary to the cellular messenger RNA transcripts of mdr genes and show that high-level expression of a full-length complementary DNA clone in an otherwise drug-sensitive cell confers a complete multidrug-resistant phenotype. Our results demonstrate that overexpression of a single member of the mdr group is sufficient to confer drug resistance. Furthermore, because the cDNA was isolated from a drug-sensitive cell, mutations in the primary sequence of mdr are not required to produce a multi-drug-resistance phenotype.

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Author notes

  1. Yinon Ben Neriah

    Present address: Department of Immunology, The Hebrew University, Hadassah Medical School, Jerusalem, 91010, Israel

Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine, McGill University, Montreal, Canada, H36 1Y6

    Philippe Gros

  2. Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02142, USA

    Yinon Ben Neriah

  3. Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

    James M. Croop & David E. Housman

Authors
  1. Philippe Gros
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  2. Yinon Ben Neriah
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  3. James M. Croop
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  4. David E. Housman
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Gros, P., Neriah, Y., Croop, J. et al. Isolation and expression of a complementary DNA that confers multidrug resistance. Nature 323, 728–731 (1986). https://doi.org/10.1038/323728a0

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