Accelerated publication -: Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc
Accelerated publication -: Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc
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DOI：
10.1074/jbc.c000023200
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发表时间：
2000-07-21
影响因子：
4.8
通讯作者：
Dang, CV
中科院分区：
文献类型：
--
作者：
Osthus, RC;Shim, H;Dang, CV
正常的哺乳动物细胞利用氧气产生能量，而癌细胞依靠糖酵解产生能量，因此对氧气的依赖程度较低。我们之前观察到c-Myc致癌转录因子调节乳酸脱氢酶A并诱导乳酸过量产生。因此，我们试图确定c-Myc是否控制其他调节葡萄糖代谢的基因。在过表达c-Myc的Rat1a成纤维细胞和小鼠肝脏中，葡萄糖转运蛋白GLUT1、磷酸葡萄糖异构酶、磷酸果糖激酶、甘油醛-3-磷酸脱氢酶、磷酸甘油激酶和烯醇化酶的mRNA水平升高。c-Myc直接激活编码GLUT1、磷酸果糖激酶和烯醇化酶的基因，并增加Rat1成纤维细胞的葡萄糖摄取，核运行研究证实c-Myc可提高GLUT1的转录率。我们的研究结果表明，c-Myc癌蛋白的过度表达通过激活葡萄糖代谢途径的几个组分来解除糖酵解的调节。
Unlike normal mammalian cells, which use oxygen to generate energy, cancer cells rely on glycolysis for energy and are therefore less dependent on oxygen. We previously observed that the c-Myc oncogenic transcription factor regulates lactate dehydrogenase A and induces lactate overproduction. We, therefore, sought to determine whether c-Myc controls other genes regulating glucose metabolism. In Rat1a fibroblasts and murine livers overexpressing c-Myc, the mRNA levels of the glucose transporter GLUT1, phosphoglucose isomerase, phosphofructokinase, glyceraldehyde-3-phosphate de hydrogenase, phosphoglycerate kinase, and enolase were elevated. c-Myc directly transactivates genes encoding GLUT1, phosphofructokinase, and enolase and increases glucose uptake in Rat1 fibroblasts, Nuclear run-on studies confirmed that the GLUT1 transcriptional rate is elevated by c-Myc. Our findings suggest that overexpression of the c-Myc oncoprotein deregulates glycolysis through the activation of several components of the glucose metabolic pathway.