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首页> 外文期刊>British Journal of Cancer >Fifth Gordon Hamilton-Fairley memorial lecture|[ast]|. Methotrexate resistance and gene amplification: An experimental model for the generation of cellular heterogeneity
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Fifth Gordon Hamilton-Fairley memorial lecture|[ast]|. Methotrexate resistance and gene amplification: An experimental model for the generation of cellular heterogeneity

机译：第五届戈登·汉密尔顿-费尔利纪念演讲| [上] |。甲氨蝶呤抗性和基因扩增：细胞异质性产生的实验模型

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摘要

Gene amplification is a mechanism whereby cultured animal cells and human tumours become resistant to cancer chemotherapeutic agents. This review of studies from the authors' laboratory describes properties of the acquisition of resistance to methotrexate in cultured mammalian cells by virtue of amplification of the dihydrofolate reductase gene. These properties result in a heterogeneous cell population with respect to many cell properties, including the number and stability of the amplified genes. Gene amplification results from overreplication of DNA in a single cell cycle as a result of inhibition of DNA synthesis. The cells surviving such overreplication constitute a heterogeneous population with multiple chromosomal changes, including partial or complete endoreduplication of chromosomes, as well as a variety of chromosomal rearrangements. A similar phenomenon may underlie the generation of aneuploidy in tumours, their malignant progression, and the generation of heterogeneity in the tumour cell population.
机译：基因扩增是一种机制，使培养的动物细胞和人类肿瘤对癌症化学治疗剂产生抵抗力。作者实验室的研究综述描述了通过扩增二氢叶酸还原酶基因在哺乳动物细胞中获得甲氨蝶呤抗性的特性。这些特性导致就许多细胞特性（包括扩增基因的数量和稳定性）而言，异质细胞群体。基因扩增是由于抑制DNA合成而在单个细胞周期中DNA过度复制所致。幸免于这种过度复制的细胞构成了具有多种染色体变化的异质种群，包括部分或完全染色体内复制，以及各种染色体重排。类似的现象可能是肿瘤中非整倍性的产生，其恶性进展以及肿瘤细胞群体异质性的产生的基础。

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