• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Life sciences >Transforming oncogenes regulate glucose transport by increasing transporter affinity for glucose: contrasting effects of oncogenes and heat stress in a murine marrow-derived cell line.
【24h】

Transforming oncogenes regulate glucose transport by increasing transporter affinity for glucose: contrasting effects of oncogenes and heat stress in a murine marrow-derived cell line.

机译：转化的癌基因通过增加转运蛋白对葡萄糖的亲和力来调节葡萄糖的转运：在小鼠骨髓衍生的细胞系中，癌基因和热应激的对比作用。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Transforming oncogenes often overcome the growth factor requirements of cells by activating growth factor signal transduction pathways. Increased energy utilization by transformed cells is a well known phenomenon, but whether glucose uptake is regulated at the level of the glucose transporter has not been clearly established. To determine whether cell transformation by specific oncogenes like, v-H-ras and v-abl affects the activation state of glucose transporters, bone marrow-derived IL-3-dependent 32D (clone3) cells transfected with temperature-sensitive ras and abl oncogenes were used to compare proliferative responses and glucose transporting ability of these cells with the parental cell line at permissive (32 degrees C) and non-permissive (40 degrees C) temperatures. Transformed cells showed elevated incorporation of [3H]thymidine and enhanced tyrosine kinase activity, both of which were abrogated in temperature-sensitive mutants maintained at the non-permissive temperature. Compared with control cells, 2-deoxy-D-[1-(3)H]glucose (2-DOG) uptake was not significantly different in transformed cells at the permissive temperature. However, transformation was associated with a 2-2.5-fold greater affinity of glucose transporters for glucose (Km) and this was reversed following treatment with tyrosine kinase inhibitor, genistein. Maximum velocity of glucose transport (Vmax) and membrane expression of transporters were reduced in oncogene-transformed cells. At the non-permissive temperature, glucose uptake was elevated in both control and oncogene-transformed cells. This increase in glucose transport was not associated with a change in transporter affinity for glucose, but increased Glut-1 expression was observed indicating a 'heat stress' effect that overrode the effects attributable to oncogene loss. The 'heat stress' effect was inhibited by protein synthesis inhibitor cycloheximide. These results provide evidence for intrinsic activation of glucose transporters by the transforming oncogenes ras and abl, and indicate that oncogenes and 'heat stress' regulate glucose transport by different mechanisms.
机译：转化致癌基因通常通过激活生长因子信号转导途径来克服细胞对生长因子的需求。转化细胞增加的能量利用是众所周知的现象，但是尚未明确确定葡萄糖吸收是否在葡萄糖转运蛋白水平上调节。为了确定通过特定癌基因（例如vH-ras和v-abl）进行的细胞转化是否会影响葡萄糖转运蛋白的激活状态，使用了转染了温度敏感ras和abl癌基因的骨髓来源的IL-3依赖性32D（clone3）细胞。比较这些细胞在允许温度（32摄氏度）和非允许温度（40摄氏度）下与亲本细胞系的增殖反应和葡萄糖转运能力。转化的细胞显示[3H]胸苷的掺入增加和酪氨酸激酶活性增强，在维持在非容许温度下的温度敏感突变体中，这两者均被废除。与对照细胞相比，在允许的温度下，转化细胞中2-脱氧-D- [1-（3）H]葡萄糖（2-DOG）的摄取无显着差异。然而，转化与葡萄糖转运蛋白对葡萄糖（Km）的2-2.5倍更大的亲和力相关，在酪氨酸激酶抑制剂染料木黄酮处理后，这种转化被逆转了。在致癌基因转化的细胞中，葡萄糖转运的最大速度（Vmax）和转运蛋白的膜表达降低。在非容许温度下，对照和致癌基因转化细胞中的葡萄糖摄取均升高。葡萄糖转运的这种增加与转运蛋白对葡萄糖的亲和力的变化无关，但是观察到Glut-1表达增加，表明“热应激”效应超过了致癌基因丧失的效应。蛋白质合成抑制剂环己酰亚胺抑制了“热应激”效应。这些结果为转化的癌基因ras和abl活化葡萄糖转运蛋白提供了证据，并表明癌基因和“热应激”通过不同的机制调节葡萄糖的转运。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号