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

First Author  Gros P Year  1986
Journal  Nature Volume  323
Issue  6090 Pages  728-31
PubMed ID  3022150 Mgi Jnum  J:8457
Mgi Id  MGI:56923 Doi  10.1038/323728a0
Citation  Gros P, et al. (1986) Isolation and expression of a complementary DNA that confers multidrug resistance. Nature 323(6090):728-31
abstractText  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.
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