Mitochondrial dysfunction in human breast cancer cells and their transmitochondrial cybrids
Mitochondrial dysfunction in human breast cancer cells and their transmitochondrial cybrids
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DOI：
10.1016/j.bbabio.2009.07.008
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发表时间：
2010-01-01
影响因子：
4.3
通讯作者：
Wong, Lee-Jun C.
中科院分区：
文献类型：
--
作者：
Ma, Yewei;Bai, Ren-Kui;Wong, Lee-Jun C.
在所有类型的癌症中都发现了体细胞线粒体DNA的改变。为了更好地了解线粒体在癌症发生发展中的作用及其参与的致病机制，我们使用线粒体环系统在确定的核背景下研究了癌症线粒体的作用。我们的结果表明，当细胞在半乳糖介质中受到代谢压力时，癌症线粒体会显著减少细胞的生长。乳腺癌细胞的呼吸链复合体活性、细胞耗氧量和ATP合成速率明显低于MCF-10A(10A)的正常乳腺上皮细胞。这些结果表明，在所研究的乳腺癌细胞系中存在线粒体功能降低。在含有癌症线粒体的胞质中也观察到类似的线粒体功能降低。在两个乳腺癌细胞系中也发现了新的tRNA突变，可能与观察到的线粒体功能障碍有关。我们得出结论，癌细胞中线粒体的改变可能在肿瘤的发展中发挥关键作用。(C)2009爱思唯尔B.V.保留所有权利。
Somatic mitochondrial DNA alterations have been found in all types of cancer. To better understand the role of mitochondria and their involvement in the pathogenic mechanisms of cancer development, the effects of cancer mitochondria were investigated in a defined nuclear background using a transmitochondrial cybrid system. Our results demonstrated that cancer mitochondria confer a significant reduction in cell growth when cells are metabolically stressed in a galactose medium. Activities of the respiratory chain complexes, cellular oxygen consumption, and ATP synthesis rates were found to be much lower in breast cancer cells, than those in normal breast epithelial cells of MCF-10A (10A). These results suggest that there is reduced mitochondrial function in the studied breast cancer cell lines. Similarly reduced mitochondrial function was observed in cybrids containing cancer mitochondria. Novel tRNA mutations were also identified in two breast cancer cell lines, possibly responsible for the observed mitochondrial dysfunction. We conclude that altered mitochondria in cancer cells may play a crucial role in tumor development. (C) 2009 Elsevier B.V. All rights reserved.