Distinct von Hippel-Lindau gene and hypoxia-regulated alterations in gene and protein expression patterns of renal cell carcinoma and their effects on metabolism.
Distinct von Hippel-Lindau gene and hypoxia-regulated alterations in gene and protein expression patterns of renal cell carcinoma and their effects on metabolism.
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DOI：
10.18632/oncotarget.3456
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发表时间：
2015-05-10
期刊：
影响因子：
--
通讯作者：
Seliger B
中科院分区：
文献类型：
--
作者：
Leisz S;Schulz K;Erb S;Oefner P;Dettmer K;Mougiakakos D;Wang E;Marincola FM;Stehle F;Seliger B
在过去的十年中，对细胞缺氧适应的分子机制和肾细胞癌（RCC）中“von Hippel Lindau”（VHL）蛋白的功能的认识有所增加，但关于这两个过程的基因/蛋白表达的重叠和差异的信息很少。因此，本研究的目的是解剖VHL和缺氧调节的人类肾细胞癌的代谢改变使用ome为基础的策略。通过测定葡萄糖摄取、乳酸分泌、细胞外pH、乳酸脱氢酶活性、氨基酸含量和ATP水平，分析VHL和低氧调节的改变的基因/蛋白表达模式对细胞代谢的影响。通过使用在常氧和低氧条件下培养的VHL−/VHL+ RCC细胞，鉴定了基因和蛋白质表达模式中的VHL依赖性、HIF依赖性以及VHL-/HIF非依赖性改变，并在其他RCC细胞系中进一步验证。在这些不同条件下差异表达的基因/蛋白质主要涉及细胞代谢，其伴随着改变的代谢以及VHL缺陷细胞中氨基酸丰度的变化。总之，该研究揭示了VHL功能和缺氧控制的基因和蛋白质的相似性，但也存在差异，从而证明了在这些条件下RCC代谢转换的差异。
During the last decade the knowledge about the molecular mechanisms of the cellular adaption to hypoxia and the function of the “von Hippel Lindau” (VHL) protein in renal cell carcinoma (RCC) has increased, but there exists little information about the overlap and differences in gene/protein expression of both processes. Therefore the aim of this study was to dissect VHL- and hypoxia-regulated alterations in the metabolism of human RCC using ome-based strategies. The effect of the VHL- and hypoxia-regulated altered gene/protein expression pattern on the cellular metabolism was analyzed by determination of glucose uptake, lactate secretion, extracellular pH, lactate dehydrogenase activity, amino acid content and ATP levels. By employing VHL−/VHL+ RCC cells cultured under normoxic and hypoxic conditions, VHL-dependent, HIF-dependent as well as VHL-/HIF-independent alterations in the gene and protein expression patterns were identified and further validated in other RCC cell lines. The genes/proteins differentially expressed under these distinct conditions were mainly involved in the cellular metabolism, which was accompanied by an altered metabolism as well as changes in the abundance of amino acids in VHL-deficient cells. In conclusion, the study reveals similarities, but also differences in the genes and proteins controlled by VHL functionality and hypoxia thereby demonstrating differences in the metabolic switch of RCC under these conditions.
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影响因子：
6.4
作者：
Singer, Katrin;Kastenberger, Michael;Kreutz, Marina
通讯作者：
Kreutz, Marina
DOI：
10.1016/s1570-9639(02)00547-2
发表时间：
2003-03-21
影响因子：
3.2
作者：
Lichtenfels, R;Kellner, R;Seliger, B
通讯作者：
Seliger, B
影响因子：
20.3
作者：
Manalo, DJ;Rowan, A;Semenza, GL
通讯作者：
Semenza, GL
DOI：
10.1073/pnas.1203083109
发表时间：
2012-09-11
影响因子：
11.1
作者：
van der Goot, Annemieke T.;Zhu, Wentao;Nollen, Ellen A. A.
通讯作者：
Nollen, Ellen A. A.
影响因子：
3.4
作者：
Unwin, RD;Craven, RA;Banks, RE
通讯作者：
Banks, RE