Nuclear DNA but not mtDNA controls tumor phenotypes in mouse cells
Nuclear DNA but not mtDNA controls tumor phenotypes in mouse cells
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DOI：
10.1016/j.bbrc.2004.12.105
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发表时间：
2005-02-25
影响因子：
3.1
通讯作者：
Hayashi, JI
中科院分区：
文献类型：
--
作者：
Akimoto, M;Niikura, M;Hayashi, JI
最近的研究表明，在各种人类肿瘤类型中，同质mtDNA突变的频率很高，这表明突变的mtDNA单倍型在某种程度上促进了肿瘤表型的表达。我们通过分离小鼠mtDNA缺失(p)细胞，在正常细胞和致癌物质诱导的转化体之间进行完全的mtDNA替换，直接解决了这一问题，并检测了mtDNA替换对致瘤性表达的影响，这是一种裸小鼠表型形成的肿瘤。结果表明，携带肿瘤细胞核DNA和正常细胞mtDNA的基因组嵌合体细胞表现出致瘤性，而携带正常细胞核DNA和肿瘤细胞mtDNA的基因组嵌合体细胞不表现出致瘤性。这些观察结果提供了直接证据，证明核DNA（而非mtDNA）负责致癌物质诱导的恶性转化，尽管mtDNA突变和由此产生的呼吸缺陷仍有可能影响恶性程度，如侵袭性或转移性。(C) 2004爱思唯尔公司版权所有。
Recent studies showed high frequencies of homoplasmic mtDNA mutations in various human tumor types, suggesting that the mutated mtDNA haplotypes somehow contribute to expression of tumor phenotypes. We directly addressed this issue by isolating mouse mtDNA-less (p) cells for complete mtDNA replacement between normal cells and their carcinogen-induced transformants, and examined the effect of the mtDNA replacement on expression of tumorigenicity, a phenotype forming tumors in nude mice. The results showed that genome chimera cells carrying nuclear DNA from tumor cells and mtDNA from normal cells expressed tumorigenicity, whereas those carrying nuclear DNA from normal cells and mtDNA from tumor cells did not. These observations provided direct evidence that nuclear DNA, but not mtDNA, is responsible for carcinogen-induced malignant transformation, although it remains possible that mtDNA mutations and resultant respiration defects may influence the degree of malignancy, such as invasive or metastatic properties. (C) 2004 Elsevier Inc. All rights reserved.