Amplification and expression of genes associated with multidrug resistance in mammalian cells.
Amplification and expression of genes associated with multidrug resistance in mammalian cells.
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哺乳动物细胞中与多药耐药性相关的基因的扩增和表达。
DOI：
10.1126/science.2421411
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Melera,PW
中科院分区：
文献类型：
--
作者：
Scotto,KW;Biedler,JL;Melera,PW
在临床和组织培养中观察到的多药耐药性中，受到某些细胞毒性药物攻击的细胞不仅对选择性药物产生耐药性，而且对其他看似无关的药物也产生耐药性。多药耐药表型与DNA序列扩增和大量胞浆和膜糖蛋白的过度产生有关。在中国仓鼠多药耐药细胞中，至少有两个相关基因（称为多药耐药相关基因）的差异扩增和表达改变。在多药耐药小鼠和人类细胞中，与中国仓鼠细胞中同源的基因也被扩增。这些基因的表达水平各不相同，与其拷贝数无关。此外，在中国仓鼠细胞中，对单一药物的耐药性和多药耐药性的发展密切相关，但非偶联的事件。多药耐药基因的过度表达与选择性药物的耐药程度的相关性比与多药耐药程度的相关性更好。
In multidrug resistance, which is observed clinically and in tissue culture, cells that are challenged with certain cytotoxic drugs develop resistance not only to the selective agent but also to other, seemingly unrelated, agents. The multidrug-resistant phenotype is associated with DNA sequence amplification and with the overproduction of a number of cytosolic and membrane glycoproteins. The differential amplification and altered expression of at least two related genes, termed multidrug-resistant associated genes has been shown in multidrug-resistant Chinese hamster cells. In multidrug-resistant mouse and human cells, genes homologous to those in Chinese hamster cells are also amplified. The level of expression of these genes varied and did not correlate with their copy number. Furthermore, in Chinese hamster cells, the development of resistance to a single drug and multidrug resistance were closely related, but uncoupled, events. The overexpression of the multidrug-resistant genes was better correlated with the degree of resistance to the selective agent than it was with the extent of multidrug resistance.