基因重排：一种多药耐药基因1（MDR-1）激活的新机制。
Gene rearrangement: a novel mechanism for MDR-1 gene activation.
作者信息
Mickley L A, Spengler B A, Knutsen T A, Biedler J L, Fojo T
机构信息
Medicine Branch, DCS, NCI, Bethesda, Maryland 20892, USA.
出版信息
J Clin Invest. 1997 Apr 15;99(8):1947-57. doi: 10.1172/JCI119362.
Abstract
Drug resistance, a major obstacle to cancer chemotherapy, can be mediated by MDR-1/P-glycoprotein. Deletion of the first 68 residues of MDR-1 in an adriamycin-selected cell line after a 4;7 translocation, t(4q;7q), resulted in a hybrid mRNA containing sequences from both MDR-1 and a novel chromosome 4 gene. Further selection resulted in amplification of a hybrid gene. Expression of the hybrid mRNA was controlled by the chromosome 4 gene, providing a model for overexpression of MDR-1. Additional hybrid mRNAs in other drug-selected cell lines and in patients with refractory leukemia, with MDR-1 juxtaposed 3' to an active gene, establishes random chromosomal rearrangements with overexpression of hybrid MDR-1 mRNAs as a mechanism of acquired drug resistance.
摘要
耐药性是癌症化疗的主要障碍，可由多药耐药蛋白1/ P-糖蛋白介导。在一个经阿霉素筛选的细胞系中，4号和7号染色体发生t(4q;7q)易位后，多药耐药蛋白1的前68个氨基酸残基缺失，产生了一种包含多药耐药蛋白1和一个新的4号染色体基因序列的杂合mRNA。进一步筛选导致一个杂合基因扩增。杂合mRNA的表达受4号染色体基因控制，为多药耐药蛋白1的过表达提供了一个模型。在其他药物筛选的细胞系和难治性白血病患者中，还有其他杂合mRNA，多药耐药蛋白1在一个活性基因的3'端并列，这表明随机染色体重排以及杂合多药耐药蛋白1 mRNA的过表达是获得性耐药的一种机制。
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