Multidrug-resistant phenotype cosegregates with an amplified gene in somatic cell hybrids of drug-resistant Chinese hamster ovary cells and drug-sensitive murine cells.
Multidrug-resistant phenotype cosegregates with an amplified gene in somatic cell hybrids of drug-resistant Chinese hamster ovary cells and drug-sensitive murine cells.
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多重耐药表型与耐药中国仓鼠卵巢细胞和药物敏感小鼠细胞的体细胞杂交体中的扩增基因共分离。
DOI：
10.1128/mcb.6.12.4268-4273.1986
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发表时间：
1986
影响因子：
5.3
通讯作者：
Kuo,MT
中科院分区：
文献类型：
--
作者：
Teeter,LD;Sanford,JA;Sen,S;Stallings,RL;Siciliano,MJ;Kuo,MT
在中国仓鼠卵巢(CHO)细胞系中，基因扩增与多药耐药(MDR)有关，这些细胞系对其他无关的细胞毒药物表现出交叉耐药。原位杂交研究(Teeter等人，J.Cell Biol，正在出版)表明，在长春新碱耐药细胞中，与MDR表型相关的扩增基因存在于长春新碱耐药细胞中最大的CHO染色体(1或Z1)的长臂上。本研究以长春新碱耐药的CHO细胞和药物敏感的小鼠细胞为材料，构建体细胞杂交瘤细胞系，以确定携带扩增序列的染色体与多药耐药表型之间的功能关系。杂交种表现为不完全显性的原发耐药和多药耐药。杂种无性系和亚无性系分离了CHO染色体。长春新碱抗性、多药耐药表型、多药耐药相关扩增序列的存在、位于这些序列中的基因的过度表达以及CHO染色体Z1之间的分离与长春新碱耐药CHO细胞的Z1染色体上存在与MDR有关的扩增基因的假设是一致的。CHO染色体Z8和2与耐药表型的不一致性较低，提示这些染色体可能含有与MDR表型相关的基因。
Gene amplification has been associated with multidrug resistance (MDR) in several drug-resistant Chinese hamster ovary (CHO) cell lines which exhibit cross-resistance to other unrelated, cytotoxic drugs. In situ hybridization studies (Teeter et al., J. Cell Biol., in press) suggested the presence of an amplified gene associated with the MDR phenotype on the long arm of either of the largest CHO chromosomes (1 or Z1) in vincristine-resistant cells. In this study, somatic cell hybrids were constructed between these vincristine-resistant CHO cells and drug-sensitive murine cells to determine the functional relationship between the chromosome bearing the amplified sequences and the MDR phenotype. Hybrids exhibited primary drug resistance and MDR in an incomplete dominant fashion. Hybrid clones and subclones segregated CHO chromosomes. Concordant segregation between vincristine resistance, the MDR phenotype, the presence of the MDR-associated amplified sequences, overexpression of the gene located in those sequences, and CHO chromosome Z1 was consistent with the hypothesis that there is an amplified gene on chromosome Z1 of the vincristine-resistant CHO cells which is responsible for the MDR in these cells. A low level of discordance between CHO chromosomes Z8 and 2 and the drug resistance phenotype suggests that these chromosomes may contain genes involved with the MDR phenotype.