Isolation and expression of a complementary DNA that confers multidrug resistance

Nature. 1986 Oct 23-29;323(6090):728-31. doi: 10.1038/323728a0.

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 or gp170. 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 multidrug-resistance phenotype.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Cricetinae
  • DNA / isolation & purification*
  • DNA Restriction Enzymes / metabolism
  • Drug Resistance / genetics*
  • Gene Expression Regulation*
  • Globins / genetics
  • Phenotype
  • RNA, Messenger / metabolism
  • Transfection

Substances

  • RNA, Messenger
  • Globins
  • DNA
  • DNA Restriction Enzymes