ISOLATION AND EXPRESSION OF A COMPLEMENTARY-DNA THAT CONFERS MULTIDRUG RESISTANCE
ISOLATION AND EXPRESSION OF A COMPLEMENTARY-DNA THAT CONFERS MULTIDRUG RESISTANCE
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DOI：
10.1038/323728a0
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发表时间：
1986-10-23
期刊：
影响因子：
64.8
通讯作者：
HOUSMAN, DE
中科院分区：
文献类型：
--
作者：
GROS, P;BEN-NERIAH, Y;HOUSMAN, DE
对多种药物具有抗性的肿瘤细胞群体的出现和生长是癌症化学治疗中的主要问题。我们使用体外培养的高耐药细胞系来研究多药耐药的分子基础。在这些细胞系中，高水平的耐药性通常与一小组名为mdr（参考文献1-3）的基因orgp 170（参考文献4）的扩增和过表达相关。这些基因在多药耐药中的作用的直接评估一直在等待这个基因家族的成员在生物活性形式的分离。在这里，我们报告的DNA克隆互补的细胞信使RNA转录ofmdr基因的分离和显示，高水平表达的全长互补DNA克隆在其他药物敏感细胞赋予一个完整的多药耐药表型。我们的研究结果表明，过量表达的一个成员的drgroup是足以赋予耐药性。此外，由于cDNA是从药物敏感细胞中分离的，mdr 1级序列的突变不需要产生多药耐药表型。
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 developedin vitroto 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 termedmdr(refs 1–3) orgp170(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 ofmdrgenes 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 themdrgroup is sufficient to confer drug resistance. Furthermore, because the cDNA was isolated from a drug-sensitive cell, mutations in the primary sequence ofmdrare not required to produce a multi-drug-resistance phenotype.