Mitochondrial genome instability resulting from SUV3 haploinsufficiency leads to tumorigenesis and shortened lifespan
Mitochondrial genome instability resulting from SUV3 haploinsufficiency leads to tumorigenesis and shortened lifespan
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DOI：
10.1038/onc.2012.120
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发表时间：
2013-02-28
期刊：
影响因子：
8
通讯作者：
Lee, W-H
中科院分区：
文献类型：
--
作者：
Chen, P-L;Chen, C-F;Lee, W-H
线粒体功能障碍一直是癌症的一个标志。然而，它是否具有致病作用还有待阐明。在这里，我们使用一个来源于线粒体解旋酶SUV3失活的动物模型，证明mSuv3+/-小鼠携带线粒体DNA （mtDNA）突变增加，mtDNA拷贝数减少，导致肿瘤在各个部位发展并缩短寿命。这些表型是母系遗传的，表明线粒体的病因作用。重要的是，在两个独立的队列中，与相应的正常组织相比，在人乳腺肿瘤标本中观察到SUV3表达降低。这些结果首次证明了通过SUV3解旋酶维持mtDNA的完整性对肿瘤抑制至关重要。中华肿瘤杂志（2013）32 (2):1193-1201；doi: 10.1038 / onc.2012.120;2012年5月7日在线发布
Mitochondrial dysfunction has been a hallmark of cancer. However, whether it has a causative role awaits to be elucidated. Here, using an animal model derived from inactivation of SUV3, a mitochondrial helicase, we demonstrated that mSuv3+/- mice harbored increased mitochondrial DNA (mtDNA) mutations and decreased mtDNA copy numbers, leading to tumor development in various sites and shortened lifespan. These phenotypes were transmitted maternally, indicating the etiological role of the mitochondria. Importantly, reduced SUV3 expression was observed in human breast tumor specimens compared with corresponding normal tissues in two independent cohorts. These results demonstrated for the first time that maintaining mtDNA integrity by SUV3 helicase is critical for cancer suppression. Oncogene (2013) 32, 1193-1201; doi:10.1038/onc.2012.120; published online 7 May 2012