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RENAL CELL CARCINOMA AND NORMAL KIDNEY PROTEIN EXPRESSION

机译:肾细胞癌和正常肾脏蛋白表达

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摘要

Renal cell carcinoma (RCC), a human kidney cancer from the proximal tubular epithelium, accounts for about 3% of adult malignancies. Molecular and cytogenetic analysis have highlighted deletions, translocations, or loss of heterozygosity in the 3p21-p26, a putative RCC locus, as well as in 6q, 8p, 9pq, and 14pq. Studies on phenotypic expression of human kidney tissue and on post-translational modifications in RCC have not yet provided a marker for early renal cell carcinoma diagnosis. Current dignostic methods do not help to detect the tumor before advanced stages. We therefore used two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) to study normal and tumor kidney tissues in ten patients suffering from RCC. A human kidney protein map in the SWISS-2DPAGE database accessible through the ExPASy WWW Molecular Biology Server was established. Of 2789 separated polypeptides, 43 were identified by gel comparison, amino acid analysis, N-terminal sequencing, and/or immunodetection. The comparison between normal and tumor kidney tissues showed four polypeptides to be absent in RCC. One of them was identified as ubiquinol cytochrome c reductase (UQCR), whose locus has elsewhere been tentatively assigned to chromosome 19p12 or chromosome 22. A second polypeptide was identified as mitochondrial NADH-ubiquinone oxidoreductase complex I whose locus is located on chromosome 18p11.2 and chromosome 19q13.3. These result suggest that the lack of UQCR and of mitochondrial NADH-ubiquinone oxidoreductase complex I expression in RCC may be caused by unknown deletions, or by changes in gene transcription or translation. It might indicate that mitochondrial disfunction plays a major role in RCC genesis or evolution. [References: 42]
机译:肾细胞癌(RCC)是来自近端肾小管上皮的人肾癌,约占成人恶性肿瘤的3%。分子和细胞遗传学分析突出显示了3p21-p26(假定的RCC基因座)以及6q,8p,9pq和14pq中杂合性的缺失,易位或缺失。人肾组织的表型表达和RCC中翻译后修饰的研究尚未为早期肾细胞癌的诊断提供标志。当前的诊断方法无助于在晚期之前检测出肿瘤。因此,我们使用二维聚丙烯酰胺凝胶电泳(2-D PAGE)研究了10例RCC患者的正常和肿瘤肾脏组织。通过ExPASy WWW分子生物学服务器可访问的SWISS-2DPAGE数据库中建立了人类肾脏蛋白图谱。在2789个分离的多肽中,通过凝胶比较,氨基酸分析,N端测序和/或免疫检测鉴定了43个。正常和肿瘤肾脏组织之间的比较显示,RCC中不存在四种多肽。其中一个被鉴定为泛醇细胞色素C还原酶(UQCR),其基因座已在其他地方暂定为19p12或22号染色体。第二个多肽被鉴定为线粒体NADH-泛醌氧化还原酶复合体I,其基因座位于18p11.2染色体上。和染色体19q13.3。这些结果表明,RCC中缺乏UQCR和线粒体NADH-泛醌氧化还原酶复合物I的表达可能是由于未知的缺失或基因转录或翻译的改变所致。这可能表明线粒体功能障碍在RCC的发生或发展中起主要作用。 [参考:42]

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