Savagner Frédérique, Mirebeau Delphine, Jacques Caroline, Guyetant Serge, Morgan Catherine, Franc Brigitte, Reynier Pascal, Malthièry Yves
INSERM EMI-U 00-18, Laboratoire de Biochimie et Biologie Moléculaire, CHU, Angers, France.
Biochem Biophys Res Commun. 2003 Oct 24;310(3):779-84. doi: 10.1016/j.bbrc.2003.09.076.
Thyroid oncocytomas are tumors characterized by dense mitochondrial accumulation, the cause of which is currently unknown. Members of the PGC-1 coactivator family have been identified as important mediators of mitochondrial biogenesis because of their ability to activate nuclear genes encoding mitochondrial proteins. We have investigated the influence of the PGC-1 related coactivator (PRC) on the high mitochondrial content observed in oncocytoma by quantifying the transcripts of PRC, the nuclear respiratory factor 1 (NRF-1) and the mitochondrial transcription factor A (TFAM), in 30 oncocytic tumors and corresponding normal tissues. The three genes studied were found to be significantly overexpressed in thyroid oncocytomas, concomitantly with an increase in cytochrome oxidase activity and mitochondrial DNA (mtDNA) content. However, no mtDNA variant in the D-loop region appeared to be involved in oncocytic development. We conclude that overexpression of the PRC pathway is responsible for mitochondrial proliferation in the context of thyroid oncocytoma.
甲状腺嗜酸细胞瘤是一种以密集的线粒体聚集为特征的肿瘤，其病因目前尚不清楚。PGC-1共激活因子家族成员已被确定为线粒体生物发生的重要介质，因为它们能够激活编码线粒体蛋白的核基因。我们通过定量30例嗜酸细胞瘤及相应正常组织中PGC-1相关共激活因子（PRC）、核呼吸因子1（NRF-1）和线粒体转录因子A（TFAM）的转录本，研究了PRC对嗜酸细胞瘤中观察到的高线粒体含量的影响。研究发现，所研究的这三个基因在甲状腺嗜酸细胞瘤中显著过表达，同时细胞色素氧化酶活性和线粒体DNA（mtDNA）含量增加。然而，D环区域的mtDNA变异似乎与嗜酸细胞的发育无关。我们得出结论，PRC途径的过表达是甲状腺嗜酸细胞瘤中线粒体增殖的原因。
