Induction of IGF-1R expression by EGR-1 facilitates the growth of prostate cancer cells
Induction of IGF-1R expression by EGR-1 facilitates the growth of prostate cancer cells
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EGR-1诱导IGF-1R表达促进前列腺癌细胞的生长
DOI：
10.1016/j.canlet.2011.11.021
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发表时间：
2012-04-28
期刊：
影响因子：
9.7
通讯作者：
Xiao, Weihua
中科院分区：
文献类型：
--
作者：
Ma, Yang;Cheng, Qinqin;Xiao, Weihua
转录因子早期生长反应-1（EGR-1）在人前列腺肿瘤中过表达，并通过未知机制促进前列腺癌进展。在这里，我们报告说，EGR-1的转录调节胰岛素样生长因子-1受体（IGF-1 R），这是在原发性前列腺癌中高度表达的表达。我们发现EGR-1的异位表达导致IGF-1 R表达增加，而EGR-1的敲低导致IGF-1 R表达显著降低。染色质免疫沉淀（ChIP）和报告基因分析结果表明，EGR-1可直接与人IGF-1 R基因结合，并能激活靶基因的表达。EGR-1通过调节IGF-1 R激活Erk和Akt通路，从而促进前列腺癌细胞的生长。综上所述，这些结果表明，EGR-1可能通过上调IGF-1 R刺激前列腺癌细胞生长，并表明EGR-1的下调可能是一种有效的治疗前列腺癌的方法。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
The transcription factor Early Growth Response-1 (EGR-1) is overexpressed in human prostate tumors and contributes to prostate cancer progression through an unknown mechanism. Here we report that EGR-1 transcriptionally regulates the expression of insulin-like growth factor-1 receptor (IGF-1R), which is highly expressed in primary prostate cancer. We find that ectopic expression of EGR-1 causes increase in IGF-1R expression, while knockdown of EGR-1 leads to dramatically decrease in IGF-1R expression. Results from chromatin immunoprecipitation (ChIP) and reporter assay show that the EGR-1 directly binds to the human IGF-1R gene and triggers the target gene expression. EGR-1 activates Erk and Akt pathway through regulation of IGF-1R, and thus promote prostate cancer cell growth. Taken together, these results suggest that EGR-1 may stimulate prostate cancer cell growth through up-regulation of IGF-1R and indicate that down-regulation of EGR-1 could be an effective therapeutic approach against prostate cancer. (C) 2011 Elsevier Ireland Ltd. All rights reserved.