Isolation and expression of a complementary DNA that confers multidrug resistance.

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.

journal_name

Nature

journal_title

Nature

authors

Gros P,Ben Neriah YB,Croop JM,Housman DE

doi

10.1038/323728a0

subject

Has Abstract

pub_date

1986-10-23 00:00:00

pages

728-31

issue

6090

eissn

0028-0836

issn

1476-4687

journal_volume

323

pub_type

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