ELEVATED LEVELS OF GLUCOSE-TRANSPORT AND TRANSPORTER MESSENGER-RNA ARE INDUCED BY RAS OR SRC ONCOGENES
ELEVATED LEVELS OF GLUCOSE-TRANSPORT AND TRANSPORTER MESSENGER-RNA ARE INDUCED BY RAS OR SRC ONCOGENES
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DOI：
10.1126/science.3103217
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发表时间：
1987-03-20
期刊：
影响因子：
56.9
通讯作者：
LODISH, HF
中科院分区：
文献类型：
--
作者：
FLIER, JS;MUECKLER, MM;LODISH, HF
葡萄糖转运速率加快是细胞转化最具特征的生化标志之一。为了研究转运蛋白活性改变的分子机制，使用了转染激活的 myc、ras 或 src 癌基因的培养啮齿动物成纤维细胞。在myc转染的细胞中，2-脱氧-D-葡萄糖摄取率没有变化。然而，在用激活的ras和src癌基因转染的细胞中，葡萄糖摄取率显着增加。 ras 和 src 转染细胞中转运速率的增加与葡萄糖转运蛋白数量的显着增加（通过免疫印迹评估）以及葡萄糖转运蛋白信使 RNA 丰度的显着增加相平行。将对照细胞暴露于促进肿瘤的佛波醇酯 12-O-十四烷酰基佛波醇-13-乙酸酯 (TPA) 18 小时，也能产生类似的效果，增加葡萄糖转运速率和转运蛋白信使 RNA 的丰度。对于ras、src和TPA，负责转运系统激活的主要机制是编码葡萄糖转运蛋白的结构基因的表达增加。
An accelerated rate of glucose transport is among the most characteristic biochemical markers of cellular transformation. To study the molecular mechanism by which transporter activity is altered, cultured rodent fibroblasts transfected with activated myc, ras, or src oncogenes were used. In myc-transfected cells, the rate of 2-deoxy-D-glucose uptake was unchanged. However, in cells transfected with activated ras and src oncogenes, the rate of glucose uptake was markedly increased. The increased transport rate in ras- and src-transfected cells was paralleled by a marked increase in the amount of glucose transporter protein, as assessed by immunoblots, as well as by a markedly increased abundance of glucose transporter messenger RNA. Exposure of control cells to the tumor-promoting phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) for 18 hours had a similar effect of increasing the rate of glucose transport and the abundance of transporter messenger RNA. For ras, src, and TPA, the predominant mechanism responsible for activation of the transport system is increased expression of the structural gene encoding the glucose transport protein.