Abril Jesús, de Heredia Miguel López, González Laura, Clèries Ramon, Nadal Marga, Condom Enric, Aguiló Fernando, Gómez-Zaera Montserrat, Nunes Virginia
Centre de Genètica Mèdica i Molecular-IDIBELL, Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona, Spain.
Prostate. 2008 Jul 1;68(10):1086-96. doi: 10.1002/pros.20771.
Prostate cancer is one of the commonest cancers worldwide and is responsible for nearly 6% of all male cancer deaths. Despite this relevance, the mechanisms involved in the development and progression of this malignancy remain unknown. The involvement of polypeptides of the mitochondrial respiratory chain, the Krebs cycle and the glutathione antioxidant system in this type of cancer has been previously described, although no publication has focused on the expression of mitochondrial genes in the prostate of PCa patients.
We have determined by reverse transcription-quantitative PCR (RT-qPCR) the relative amount of the transcripts of eight mitochondrial genes (MT-ND2, MT-ND4, MT-ND6, MT-CYB, 12S/MT-RNR1, 16S/MT-RNR2, MT-CO2/COX2, MT-ATP6), and four nuclear genes (COX11, GSR, CS, ACO2), all of them key players in the normal metabolism of mitochondria. Additionally we analyzed the expression of Cyclophilin A (PPIA).
We observed differential expression of mitochondrial 12S/MT-RNR1, MT-CO2/COX2, and MT-ATP6 transcripts in tumor samples when compared to their paired normal samples.
The amount of mitochondrial 12S/MT-RNR1, MT-CO2/COX2, and MT-ATP6 transcripts is significantly decreased in tumor samples when compared to their paired normal sample, suggesting that mitochondrial gene expression is altered in PCa.
前列腺癌是全球最常见的癌症之一,占男性癌症死亡总数的近6%。尽管具有这种相关性,但这种恶性肿瘤发生和发展所涉及的机制仍然未知。此前已有文献描述了线粒体呼吸链、三羧酸循环和谷胱甘肽抗氧化系统的多肽在这类癌症中的作用,不过尚无关于前列腺癌患者前列腺中线粒体基因表达的报道。
我们通过逆转录定量聚合酶链反应(RT-qPCR)测定了八个线粒体基因(MT-ND2、MT-ND4、MT-ND6、MT-CYB、12S/MT-RNR1、16S/MT-RNR2、MT-CO2/COX2、MT-ATP6)以及四个核基因(COX11、GSR、CS、ACO2)的转录本相对含量,这些基因都是线粒体正常代谢中的关键因子。此外,我们还分析了亲环蛋白A(PPIA)的表达。
与配对的正常样本相比,我们观察到肿瘤样本中线粒体12S/MT-RNR1、MT-CO2/COX2和MT-ATP6转录本的表达存在差异。
与配对的正常样本相比,肿瘤样本中线粒体12S/MT-RNR1、MT-CO2/COX2和MT-ATP6转录本的数量显著减少,这表明前列腺癌中线粒体基因表达发生了改变。