Alteration of the copy number and deletion of mitochondrial DNA in human hepatocellular carcinoma.
Alteration of the copy number and deletion of mitochondrial DNA in human hepatocellular carcinoma.
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DOI：
10.1038/sj.bjc.6601838
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发表时间：
2004-06-14
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
在肝细胞癌（HCC）中检测到线粒体DNA （mtDNA）的体细胞突变。然而，目前尚不清楚mtDNA拷贝数和线粒体生物发生是否在HCC中发生改变。在这项研究中，我们发现与相应的非肿瘤肝脏相比，hcc的mtDNA拷贝数和线粒体呼吸蛋白含量减少。MtDNA拷贝数在女性HCC中显著减少，而在男性HCC中无显著减少。HCC中过氧化物酶体增殖物激活受体γ共激活因子-1的表达显著抑制（P<0.005），而线粒体单链dna结合蛋白的表达上调，表明HCC中线粒体生物发生的调控受到干扰。此外，22%的hcc在mtDNA d -环区携带体细胞突变。有长期饮酒史的HCC患者的非瘤性肝脏mtDNA拷贝数较非饮酒患者减少（P<0.05）， 4977 bp缺失mtDNA水平较高（P<0.05）。我们的研究结果表明，mtDNA拷贝数减少、线粒体生物发生受损和mtDNA体细胞突变是HCC癌变过程中的重要事件，男性和女性HCC mtDNA的差异改变可能是女性和男性HCC患者临床表现差异的原因。
Somatic mutations in mitochondrial DNA (mtDNA) have been detected in hepatocellular carcinoma (HCC). However, it remains unclear whether mtDNA copy number and mitochondrial biogenesis are altered in HCC. In this study, we found that mtDNA copy number and the content of mitochondrial respiratory proteins were reduced in HCCs as compared with the corresponding non-tumorous livers. MtDNA copy number was significantly reduced in female HCC but not in male HCC. Expression of the peroxisome proliferator-activated receptor γ coactivator-1 was significantly repressed in HCCs (P<0.005), while the expression of the mitochondrial single-strand DNA-binding protein was upregulated, indicating that the regulation of mitochondria biogenesis is disturbed in HCC. Moreover, 22% of HCCs carried a somatic mutation in the mtDNA D-loop region. The non-tumorous liver of the HCC patients with a long-term alcohol-drinking history contained reduced mtDNA copy number (P<0.05) and higher level of the 4977 bp-deleted mtDNA (P<0.05) as compared with non-alcohol patients. Our results suggest that reduced mtDNA copy number, impaired mitochondrial biogenesis and somatic mutations in mtDNA are important events during carcinogenesis of HCC, and the differential alterations in mtDNA of male and female HCC may contribute to the differences in the clinical manifestation between female and male HCC patients.
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影响因子：
29.4
作者：
Demeilliers, C;Maisonneuve, C;Fromenty, B
通讯作者：
Fromenty, B
影响因子：
8
作者：
Singh, KK;Russell, J;Keshav, KF
通讯作者：
Keshav, KF
影响因子：
3.5
作者：
TOYOKUNI, S;OKAMOTO, K;HIAI, H
通讯作者：
HIAI, H
影响因子：
64.5
作者：
Wu, ZD;Puigserver, P;Spiegelman, BM
通讯作者：
Spiegelman, BM
DOI：
10.1016/j.mrfmmm.2003.12.011
发表时间：
2004-03-22
影响因子：
2.3
作者：
Lee, HC;Li, SH;Wei, YH
通讯作者：
Wei, YH