Ueda K, Cardarelli C, Gottesman M M, Pastan I
Proc Natl Acad Sci U S A. 1987 May;84(9):3004-8. doi: 10.1073/pnas.84.9.3004.
Intrinsic and acquired multidrug resistance (MDR) is an important problem in cancer therapy. MDR in human KB carcinoma cells selected for resistance to colchicine, vinblastine, or doxorubicin (former generic name adriamycin) is associated with overexpression of the "MDR1" gene, which encodes P-glycoprotein. We previously have isolated an overlapping set of cDNA clones for the human MDR1 gene from multidrug-resistant KB cells. Here we report the construction of a full-length cDNA for the human MDR1 gene and show that this reconstructed cDNA, when inserted into a retroviral expression vector containing the long terminal repeats of Moloney leukemia virus or Harvey sarcoma virus, functions in mouse NIH 3T3 and human KB cells to confer the complete multidrug-resistance phenotype. These results suggest that the human MDR1 gene may be used as a positive selectable marker to introduce genes into human cells and to transform human cells to multidrug resistance without introducing nonhuman antigens.
内在性和获得性多药耐药（MDR）是癌症治疗中的一个重要问题。对秋水仙碱、长春碱或阿霉素（以前的通用名阿霉素）产生耐药性的人KB癌细胞中的MDR与“MDR1”基因的过表达有关，该基因编码P-糖蛋白。我们之前已经从多药耐药的KB细胞中分离出了一组重叠的人MDR1基因cDNA克隆。在此我们报告了人MDR1基因全长cDNA的构建，并表明当将这种重建的cDNA插入含有莫洛尼白血病病毒或哈维肉瘤病毒长末端重复序列的逆转录病毒表达载体中时，它在小鼠NIH 3T3细胞和人KB细胞中发挥作用，赋予完全的多药耐药表型。这些结果表明，人MDR1基因可用作阳性选择标记，将基因导入人细胞并将人细胞转化为多药耐药，而不引入非人类抗原。
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