Differences in nuclear gene expression between cells containing monomer and dimer mitochondrial genomes
Differences in nuclear gene expression between cells containing monomer and dimer mitochondrial genomes
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DOI：
10.1016/s0378-1119(01)00805-8
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发表时间：
2002-03-06
期刊：
影响因子：
3.5
通讯作者：
Clayton, DA
中科院分区：
文献类型：
--
作者：
Clark, KM;Brown, TA;Clayton, DA
已知哺乳动物线粒体DNA（mtDNA）的点突变和重排（缺失和重复）可导致线粒体功能障碍和人类疾病。尽管mtDNA环状二聚体与人类肿瘤密切相关，但很少有人关注mtDNA环状二聚体（由两个基因组首尾相连组成的复杂形式）。线粒体DNA二聚体经常在人类白血病中发现，但其存在的临床相关性仍然未知。为了开始研究环状二聚体mtDNA在致瘤表型中的作用，我们建立了含有单体和二聚体线粒体基因组的等基因细胞系，并使用Affyphase基因阵列分析比较了各自的核mRNA表达。令人惊讶的是，观察到大量的核基因变化，其中最大类别的基因之一与细胞表面和细胞外基质的重塑有关。由于细胞生长、迁移、凋亡和许多其他细胞过程受到来自细胞表面的信号的影响，因此与mtDNA二聚体存在相关的变化可能导致致瘤潜力和/或进展的显著改变。(C)2002 Elsevier Science B. V.保留所有权利。
It is known that point mutations and rearrangements (deletions and duplications) of mammalian mitochondrial DNA (mtDNA) can result in mitochondrial dysfunction and human disease. Very little attention has been paid to mtDNA circular dimers (a complex form consisting of two genomes joined head-to-tail) despite their close association with human neoplasia. MtDNA dimers are frequently found in human leukemia, but the clinical relevance of their presence remains unknown. To begin to investigate the role of circular dimer mtDNA in the tumorigenic phenotype, we have created isogenic cell lines containing monomer and dimer mitochondrial genomes and compared the respective nuclear mRNA expression using Affymetrix gene array analysis. Surprisingly, a large number of nuclear gene changes were observed, with one of the largest category of genes being associated with remodeling of the cell surface and extracellular matrix. Since cell growth, migration, apoptosis, and many other cellular processes are influenced by signals initiating from the cell surface, the changes associated with the presence of mtDNA dimers could lead to significant alterations in tumorigenic potential and/or progression. (C) 2002 Elsevier Science B.V. All rights reserved.