GENETIC ANALYSIS OF THE MULTIDRUG RESISTANCE PHENOTYPE IN TUMOR CELLS

对人类癌症的化疗耐药性进行了研究 建立模拟发育的体外和体内遗传系统 抗药性。人类多药耐药的主要机制 肿瘤是我们已经克隆和测序的mdr1基因的表达。 逆转录病毒载体携带的mdr1基因的表达可用于 将细胞转化为多药耐药，并已被用于授予 体外和体内对小鼠骨髓细胞的耐药性。机械论 对P-糖蛋白的研究表明，它与药物的清除有关 直接从质膜中提取。为了研究机制，我们已经生成了 许多突变体和启动了包括提纯在内的生化研究 P-糖蛋白表达与药物依赖性ATPase活性的重建 人工脂质体。

Resistance to chemotherapy of human cancers has been studied by establishing in vitro and in vivo genetic systems which mimic development of drug resistance. A major mechanism of multidrug resistance in human cancer is expression of the MDR1 gene which we have cloned and sequenced. Expression of the MDR1 gene carried by retroviral vectors can be used to transduce cells to multidrug resistance and has been used to confer resistance to mouse bone marrow cells in vitro and in vivo. Mechanistic studies on P-glycoprotein suggest that it is involved in removing drug directly from the plasma membrane. To study mechanism, we have generated many mutants and initiated biochemical studies including the purification of P-glycoprotein and reconstruction of drug-dependent ATPase activity in artificial liposomes.