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肾细胞癌中线粒体DNA含量及能量代谢的降低

Decrease of mitochondrial DNA content and energy metabolism in renal cell carcinoma.

作者信息

Meierhofer David, Mayr Johannes A, Foetschl Ulrike, Berger Alexandra, Fink Klaus, Schmeller Nikolaus, Hacker Gerhard W, Hauser-Kronberger Cornelia, Kofler Barbara, Sperl Wolfgang

机构信息

Department of Pediatrics, Paracelsus Private Medical University Salzburg, Muellner Hauptstr. 48, A-5020 Salzburg, Austria.

出版信息

Carcinogenesis. 2004 Jun;25(6):1005-10. doi: 10.1093/carcin/bgh104. Epub 2004 Feb 4.

Abstract

To elucidate the relationship between tumor genesis and the mitochondrial energy metabolism in renal neoplasms, we studied three individual enzyme activities of the oxidative phosphorylation, two components of the Krebs cycle and the mitochondrial DNA content of renal carcinomas including 29 conventional, five papillary, two unclassified carcinomas with sarcomatoid features and one collecting duct carcinoma. A significant reduction of all mitochondrial enzyme activities including complex V, as well as of the mitochondrial DNA content was detected in 34 of 37 renal carcinoma tissues as compared with control kidney. Mitochondrial enzyme activities and mitochondrial DNA levels were not statistically different between the conventional, papillary and unclassified sarcomatoid type of renal carcinoma and did not correlate with tumour grade, metastasis, ploidy and proliferative activity as determined by Ki-67 staining. Taken together, our data indicate that a co-ordinated down-regulation of all components necessary for mitochondrial energy metabolism occurs in most renal carcinomas as an early event in carcinoma formation, which does not change with progression of the disease.

摘要

为阐明肾肿瘤发生与线粒体能量代谢之间的关系,我们研究了氧化磷酸化的三种个体酶活性、三羧酸循环的两个组分以及肾癌的线粒体DNA含量,其中包括29例传统型、5例乳头状、2例具有肉瘤样特征的未分类癌以及1例集合管癌。与对照肾相比,在37例肾癌组织中的34例中检测到包括复合物V在内的所有线粒体酶活性以及线粒体DNA含量均显著降低。传统型、乳头状和未分类肉瘤样型肾癌之间的线粒体酶活性和线粒体DNA水平无统计学差异,且与通过Ki-67染色确定的肿瘤分级、转移、倍体和增殖活性无关。综上所述,我们的数据表明,线粒体能量代谢所需的所有组分的协同下调在大多数肾癌中作为癌形成的早期事件发生,且不随疾病进展而改变。

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