Isolation and expression of a complementary DNA that confers multidrug resistance.
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.
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000302:isolation & purification*; D004262:DNA Restriction Enzymes / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics*; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection
D012333:RNA, Messenger; D005914:Globins; D004247:DNA; D004262:DNA Restriction Enzymes