顺铂选择线粒体 DNA OriB 变体（16184-16193 多嘧啶序列）的短链形式，这些形式赋予顺铂耐药性。
Cisplatin selects short forms of the mitochondrial DNA OriB variant (16184-16193 poly-cytosine tract), which confer resistance to cisplatin.
机构信息
Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan.
Department of Applied Chemistry, National Defense Academy, 1-10-20 Hashirimizu, Yokosuka 239-8686, Japan.
出版信息
Sci Rep. 2017 Apr 10;7:46240. doi: 10.1038/srep46240.
A number of alternations in mitochondrial DNA (mtDNA) have been reported in different types of cancers, and the role of mtDNA in cancer has been attracting increasing interest. In order to investigate the relationship between mtDNA alternations and chemosensitivity, we constructed cybrid (trans-mitochondrial hybrid) cell lines carrying a HeLa nucleus and the mtDNA of healthy individuals because of the presence of somatic alternations in the mtDNA of many cancer cells. After a treatment with 1.0 μg/mL cisplatin for 10 days, we isolated 100 cisplatin-resistant clones, 70 of which carried the shorter mtDNA OriB variant (16184-16193 poly-cytosine tract), which was located in the control region of mtDNA. Whole mtDNA sequencing of 10 clones revealed no additional alternations. Re-construction of the HeLa nucleus and mtDNA from cisplatin-resistant cells showed that cisplatin resistance was only acquired by mtDNA alternations in the control region, and not by possible alternation(s) in the nuclear genome.
已有多项研究报道了不同类型癌症中线粒体 DNA（mtDNA）的改变，mtDNA 在癌症中的作用也越来越受到关注。为了研究 mtDNA 改变与化疗敏感性之间的关系，我们构建了携带 HeLa 细胞核和健康个体 mtDNA 的杂种（转线粒体杂种）细胞系，因为许多癌细胞的 mtDNA 中存在体细胞改变。用 1.0μg/mL 的顺铂处理 10 天后，我们分离出 100 个耐顺铂的克隆，其中 70 个携带较短的 mtDNA OriB 变体（16184-16193 多嘧啶核苷酸链），该变体位于 mtDNA 的控制区。对 10 个克隆的全 mtDNA 测序未发现其他改变。来自耐顺铂细胞的 HeLa 核和 mtDNA 的重新构建表明，顺铂耐药性仅由控制区的 mtDNA 改变获得，而不是核基因组中的可能改变。
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