Downregulation of stathmin expression is mediated directly by Egr1 and associated with p53 activity in lung cancer cell line A549
Downregulation of stathmin expression is mediated directly by Egr1 and associated with p53 activity in lung cancer cell line A549
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在肺癌细胞系 A549 中，stathmin 表达的下调由 Egr1 直接介导，并与 p53 活性相关。
DOI：
10.1016/j.cellsig.2009.09.030
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发表时间：
2010-01-01
影响因子：
4.8
通讯作者：
Zhang Huizhong
中科院分区：
文献类型：
--
作者：
Lin Fang;Long Min;Zhang Huizhong
Stathmin在多种评估的人类恶性肿瘤中过表达，并且与肿瘤进展和不良预后相关。下调其表达将有助于优化各种恶性肿瘤的治疗结果。然而，stathmin基因过表达的机制目前尚未完全阐明。早期生长反应1（Egr 1）是一种转录因子，在各种刺激下触发介导细胞生长和血管生成的下游基因的转录。在此基础上，我们通过计算机分析了Egr 1在肺癌细胞株A549中对stathmin基因表达的调控作用。结果表明，Egr 1转录因子与stathmin基因启动子5 '-GCGGGGCG-3'结合;在报告基因分析和过表达实验中，Egr 1的内源或外源表达均下调stathmin基因启动子活性和stathmin基因表达水平。使用野生型Egr 1和敲除Egr 1的细胞系，我们证明了p53通过Egr 1途径负调控stathmin表达。总之，Egr 1是stathmin表达的一种新的调节因子，p53介导了Egr 1在人肺癌细胞中对stathmin的转录抑制。(C)2009 Elsevier Inc. All rights reserved.
Stathmin is overexpressed in a variety of assessed human malignancies and is correlated with tumor progression and poor prognosis. Downregulation of its expression will contribute to optimize therapeutic outcomes in the treatment of various malignancies. However, the mechanisms of stathmin gene overexpression are not completely elucidated at present. Early growth response 1 (Egr1) is a transcription factor that triggers transcription of downstream genes mediating cell growth and angiogenesis upon various stimulations. Following the previous computational identification of a site that was thought to be an Egr1 consensus binding sequence at -85 to -94 region in stathmin gene promoter, we analyzed the role of Egr1 in the regulation of stathmin gene expression in lung cancer cell line A549. The results showed that Egr1 transcription factor bound to the sequence 5'-GCGGGGGCG-3' within human stathmin gene promoter; and in reporter gene assays and overexpression experiments, both stathmin gene promoter activity and stathmin gene expression level were downregulated following endogenous or exogenous expression of Egr1. Using wild type Egr1 and knockout Egr1 cell lines, we demonstrated that p53 negatively regulates stathmin expression through Egr1 pathway. In summary, Egr1 is a novel regulator of stathmin expression and p53 mediates the transcriptional repression of stathmin by Egr1 in human lung cancer cells. (C) 2009 Elsevier Inc. All rights reserved.