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Expression of hamster P-glycoprotein and multidrug resistance in DNA-mediated transformants of mouse LTA cells.

机译:在小鼠LTA细胞的DNA介导的转化子中,仓鼠P糖蛋白的表达和多药耐药性。

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The overexpression of a plasma membrane glycoprotein, P-glycoprotein, is strongly correlated with the expression of multidrug resistance. This phenotype (frequently observed in cell lines selected for resistance to a single drug) is characterized by cross resistance to many drugs, some of which are used in cancer chemotherapy. In the present study we showed that DNA-mediated transformants of mouse LTA cells with DNA from multidrug-resistant hamster cells acquired the multidrug resistance phenotype, that the transformants contained hamster P-glycoprotein DNA sequences, that these sequences were amplified whereas the recipient mouse P-glycoprotein sequences remained at wild-type levels, and that the overexpressed P-glycoprotein in these cells was of hamster origin. Furthermore, we showed that the hamster P-glycoprotein sequences were transfected independently of a group of genes that were originally coamplified and linked within a 1-megabase-pair region in the donor hamster genome. These data indicate that the high expression of P-glycoprotein is the only alteration required to mediate multidrug resistance.
机译:质膜糖蛋白P-糖蛋白的过表达与多药耐药性的表达密切相关。这种表型(通常在对一种药物具有抗性的细胞系中经常观察到)的特征在于对许多药物的交叉抗性,其中一些药物用于癌症化学疗法。在本研究中,我们显示了具有来自多药耐药性仓鼠细胞的DNA的小鼠LTA细胞的DNA介导的转化子具有多药耐药性表型,该转化子包含仓鼠P-糖蛋白DNA序列,这些序列被扩增,而受体小鼠P -糖蛋白序列保持在野生型水平,并且在这些细胞中过表达的P-糖蛋白是仓鼠起源的。此外,我们显示仓鼠P糖蛋白序列的转染独立于一组基因,该基因最初被共扩增并在供体仓鼠基因组的1兆碱基对区域内链接。这些数据表明,P-糖蛋白的高表达是介导多药耐药性的唯一改变。

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