Altered glucose metabolism in Harvey-ras transformed MCF10A cells.
Altered glucose metabolism in Harvey-ras transformed MCF10A cells.
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DOI：
10.1002/mc.22079
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发表时间：
2015-02
影响因子：
4.6
通讯作者：
Teegarden, Dorothy
中科院分区：
文献类型：
--
作者：
Zheng, Wei;Tayyari, Fariba;Gowda, G. A. Nagana;Raftery, Daniel;McLamore, Eric S.;Porterfield, D. Marshall;Donkin, Shawn S.;Bequette, Brian;Teegarden, Dorothy
改变葡萄糖利用的代谢重编程，包括“瓦尔堡效应”，在肿瘤发生表型的发展中至关重要。然而，Harvey-ras（H-ras）癌基因在乳腺癌发生过程中对细胞能量代谢的影响尚不清楚。本研究的目的是使用未转化的MCF 10A和H-ras癌基因转染（MCF 10A-ras）的人乳腺上皮细胞（早期乳腺癌进展的模型）来确定H-ras转化对葡萄糖代谢的影响。我们通过选择性微生物传感器测量细胞膜上的代谢物通量，通过培养基代谢物的13 C质量同位素异构体分布分析测量[13 C6]葡萄糖通量，通过NMR测量细胞内代谢物水平，通过定量PCR测量葡萄糖代谢酶的基因表达。这些研究的结果表明，MCF 10A-ras细胞表现出增强的糖酵解活性和乳酸产生，减少通过三羧酸（TCA）循环的葡萄糖通量，以及增加戊糖磷酸途径（PPP）中葡萄糖的利用。这些结果为H-ras癌基因在早期乳腺癌发生过程中MCF 10A细胞代谢重编程中的作用提供了证据。
Metabolic reprogramming that alters the utilization of glucose including the “Warburg effect” is critical in the development of a tumorigenic phenotype. However, the effects of the Harvey-ras (H-ras) oncogene on cellular energy metabolism during mammary carcinogenesis are not known. The purpose of this study was to determine the effect of H-ras transformation on glucose metabolism using the untransformed MCF10A and H-ras oncogene transfected (MCF10A-ras) human breast epithelial cells, a model for early breast cancer progression. We measured the metabolite fluxes at the cell membrane by a selective micro-biosensor, [13C6]glucose flux by 13C-mass isotopomer distribution analysis of media metabolites, intracellular metabolite levels by NMR, and gene expression of glucose metabolism enzymes by quantitative PCR. Results from these studies indicated that MCF10A-ras cells exhibited enhanced glycolytic activity and lactate production, decreased glucose flux through the tricarboxylic acid (TCA) cycle, as well as an increase in the utilization of glucose in the pentose phosphate pathway (PPP). These results provide evidence for a role of H-ras oncogene in the metabolic reprogramming of MCF10A cells during early mammary carcinogenesis.
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影响因子：
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作者：
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通讯作者：
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