Isolation and expression of a complementary DNA that confers multidrug resistance

Philippe Gros, Yinon Ben Neriah, James Croop, David E. Housman

Research output: Contribution to journalArticle

675 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)728-731
Number of pages4
JournalNature
Volume323
Issue number6090
DOIs
StatePublished - 1986
Externally publishedYes

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Multiple Drug Resistance
Complementary DNA
Pharmaceutical Preparations
Clone Cells
Genes
MDR Genes
Phenotype
Cell Line
Drug Resistance
Neoplasms
Messenger RNA
Mutation
Population

ASJC Scopus subject areas

  • General

Cite this

Isolation and expression of a complementary DNA that confers multidrug resistance. / Gros, Philippe; Neriah, Yinon Ben; Croop, James; Housman, David E.

In: Nature, Vol. 323, No. 6090, 1986, p. 728-731.

Research output: Contribution to journalArticle

Gros, Philippe ; Neriah, Yinon Ben ; Croop, James ; Housman, David E. / Isolation and expression of a complementary DNA that confers multidrug resistance. In: Nature. 1986 ; Vol. 323, No. 6090. pp. 728-731.
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