Ma Yewei, Bai Ren-Kui, Trieu Robert, Wong Lee-Jun C
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB2015, Houston, Texas 77030, USA.
Biochim Biophys Acta. 2010 Jan;1797(1):29-37. doi: 10.1016/j.bbabio.2009.07.008. Epub 2009 Aug 4.
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.
在所有类型的癌症中均发现了体细胞线粒体DNA改变。为了更好地理解线粒体的作用及其在癌症发生致病机制中的参与情况，利用线粒体转移杂交细胞系统在明确的核背景下研究了癌症线粒体的影响。我们的结果表明，当细胞在半乳糖培养基中受到代谢应激时，癌症线粒体使细胞生长显著降低。发现乳腺癌细胞中呼吸链复合物的活性、细胞耗氧量和ATP合成速率比MCF-10A（10A）正常乳腺上皮细胞中的低得多。这些结果表明，在所研究的乳腺癌细胞系中线粒体功能降低。在含有癌症线粒体的杂交细胞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还鉴定出了新的tRNA突变，这可能是观察到的线粒体功能障碍的原因。我们得出结论，癌细胞中线粒体的改变可能在肿瘤发展中起关键作用。
