Hypoxia activates the IGF-1 expression through STAT5b in human HepG2 cells
Hypoxia activates the IGF-1 expression through STAT5b in human HepG2 cells
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DOI：
10.1016/j.bbrc.2007.04.201
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发表时间：
2007-07-06
影响因子：
3.1
通讯作者：
Yang, Young Mok
中科院分区：
文献类型：
--
作者：
Joung, Youn-Hee;Lee, Moon-Young;Yang, Young Mok
胰岛素样生长因子（IGF），一种在细胞和组织中调节生长、分化和存活的多肽，在组成活性STAT5存在的情况下，可以增强来自异种和同源启动子的基因表达。这个高度保守的700 bp DNA区域包含两个位置紧密一致的stat5结合位点。缺氧通过STAT5b调控IGF-1基因的表达。我们证实在缺氧条件下STAT5b被上调，并且在HepG2细胞中，增加的STAT5b与IGF-1基因远端5'侧区域的stat5结合位点I和2强烈结合。EMSA研究表明，缺氧条件下stat5b转染的COS-7细胞中，stat5与IGF-1启动子的结合活性明显增加。缺氧也使HepG2细胞IGF-1基因表达升高。通过siRNA实验抑制STAT5b表达，导致IGF-1降低。这些结果为在实体瘤细胞中通过STAT5b-IGF-1通路治疗癌症提供了分子靶点基础。(c) 2007爱思唯尔公司版权所有。
Insulin-like growth factors (IGF), polypeptides that regulate growth, differentiation, and survival in cells and tissues, were found to enhance gene expression from both heterologous and homologous promoters in the presence of constitutively active STAT5. This highly conserved 700-bp DNA region contains two closely located consensus STAT5-binding sites. Hypoxia regulates the IGF-1 gene expression through the STAT5b. We confirmed STAT5b is up-regulated under hypoxic conditions, and the increased STAT5b binds strongly to the STAT5-binding sites I and 2 contained within the distal 5'-flanking region of IGF-1 gene in HepG2 cells. EMSA studies showed that STAT5-binding activities to the IGF-1 promoter distinctly increased under hypoxia in STAT5b-transfected COS-7 cells. The IGF-1 gene expression was also increased by hypoxia in HepG2 cells. STAT5b expression was inhibited by siRNA experiments leading to decreased IGF-1. These results provide a basis of molecular targets for cancer treatment via the STAT5b-IGF-1 pathway in solid tumor cells. (c) 2007 Elsevier Inc. All rights reserved.