EXPRESSION OF A FULL-LENGTH CDNA FOR THE HUMAN MDR1 GENE CONFERS RESISTANCE TO COLCHICINE, DOXORUBICIN, AND VINBLASTINE
EXPRESSION OF A FULL-LENGTH CDNA FOR THE HUMAN MDR1 GENE CONFERS RESISTANCE TO COLCHICINE, DOXORUBICIN, AND VINBLASTINE
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DOI：
10.1073/pnas.84.9.3004
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发表时间：
1987-05-01
影响因子：
11.1
通讯作者：
PASTAN, I
中科院分区：
文献类型：
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作者：
UEDA, K;CARDARELLI, C;PASTAN, I
内源性和获得性多药耐药（MDR）是肿瘤治疗中的一个重要问题。选择对秋水仙碱、长春碱或多柔比星（以前的通用名阿霉素）具有抗性的人KB癌细胞中的MDR与编码P-糖蛋白的“MDR 1”基因的过表达相关。我们先前已经从多药耐药KB细胞中分离出一组重叠的人MDR 1基因cDNA克隆。在这里，我们报告的人类MDR 1基因的全长cDNA的构建，并表明，这种重建的cDNA，插入到一个逆转录病毒表达载体含有长末端重复的莫洛尼白血病病毒或哈维肉瘤病毒，在小鼠NIH 3 T3和人KB细胞的功能，赋予完整的多药耐药表型。这些结果表明，人MDR 1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，而不引入非人抗原。
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.