ISOLATION OF HUMAN MDR-DNA SEQUENCES AMPLIFIED IN MULTIDRUG-RESISTANT KB CARCINOMA-CELLS
ISOLATION OF HUMAN MDR-DNA SEQUENCES AMPLIFIED IN MULTIDRUG-RESISTANT KB CARCINOMA-CELLS
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DOI：
10.1073/pnas.83.12.4538
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发表时间：
1986-06-01
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：
RONINSON, IB;CHIN, JE;PASTAN, I
肿瘤细胞对结构不同的细胞毒性药物同时产生耐药性的能力构成了癌症化疗中的主要问题。先前证明，多重耐药中国仓鼠细胞系含有扩增的转录活性DNA序列，命名为mdr。这份报告提出的证据表明，多药耐药亚系的人KB癌细胞，选择耐秋水仙碱，长春碱，或阿霉素（多柔比星），显示扩增的两个不同的DNA序列同源的仓鼠MDR基因。已克隆了人多药耐药DNA序列的片段，命名为mdr1和mdr2。mdr1序列在所有高度耐药的亚系中扩增，并表达为4.5倍酶的poly（A）+ RNA种类，在耐药细胞中检测到，但在亲本细胞系中未检测到。未检测到mdr2序列的表达。mdr2序列在一些多药耐药亚系中与mdr1共扩增，并且在两个独立衍生的细胞系中经历非常相似的重排。这些数据表明mdr1基因与人类细胞的多药耐药性有关。
The ability of tumor cells to develop simultaneous resistance to structurally different cytotoxic drugs constitute a major problem in cancer chemotherapy. It was previously demonstrated that multidrug-resistant Chinese hamster cell lines contain an amplified, transcriptionally active DNA sequence designated mdr. This report presents evidence that multidrug-resistant sublines of human KB carcinoma cells, selected for resistance to either colchicine, vinblastine, or Adriamycin (doxorubicin), display amplification of two different DNA sequences homologous to the hamster mdr gene. Segments of the human mdr DNA sequences, designated mdr1 and mdr2, have been cloned. mdr1 sequences were amplified in all of the highly drug-resistant sublines and were expressed as a poly(A)+ RNA species of 4.5 kilobases that was detected in the resistant cells but not in the parental cell line. No expression of mdr2 sequences was detected. mdr2 sequences were coamplified with mdr1 in some of the multidrug-resistant sublines and, in two independently derived cell lines, underwent very similar rearrangements. The data suggest that the mdr1 gene is involved in multidrug resistance in human cells.