Effect of exogenous E2F-1 on the expression of common chromosome fragile site genes, FHIT and WWOX
Effect of exogenous E2F-1 on the expression of common chromosome fragile site genes, FHIT and WWOX
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DOI：
10.1016/j.bbrc.2004.02.159
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发表时间：
2004-04-16
影响因子：
3.1
通讯作者：
Furukawa, Y
中科院分区：
文献类型：
--
作者：
Ishii, H;Mimori, K;Furukawa, Y
两个肿瘤抑制基因，脆性组氨酸三联体（FHIT）和WW结构域包含氧化还原酶（WWOA），包括常见的染色体脆性区域，FRA3B在3p14.2和FRA16D在16q23，在许多上皮肿瘤的表达改变。由于DNA序列搜索显示FHIT基因在5 '区具有E2F-1识别位点，其调节细胞周期，因此我们测试了E2F-1过表达在肿瘤细胞中的作用。异位E2F-1表达导致等位基因剩余肿瘤细胞中Fhit和Wwox表达增加，并导致诱导凋亡。报告基因分析表明，外源E2 F-1导入后，FHIT 5 '区的E2 F-1位点参与下游转录。染色质免疫沉淀法检测到外源性E2F-1与FHIT 5 '端识别位点的结合。这些数据表明，E2F-1过表达在肿瘤抑制中起作用，至少部分通过FHIT的转录调节和WWOX的相关激活。(C)2004爱思唯尔公司All rights reserved.
The expression of two tumor suppressor genes, fragile histidine triad (FHIT) and WW domain containing oxidoreductase (WWOA), encompassing common chromosome fragile regions, FRA3B at 3p14.2 and FRA16D at 16q23, is altered in many epithelial tumors. Since DNA sequence search shows that the FHIT gene has the E2F-1 recognition site in 5' region, which regulates cell cycle, we tested the effect of E2F-1 overexpression in tumor cells. Ectopic E2F-1 expression led to an increase of Fhit and Wwox expression in allele remaining tumor cells and resulted in induction of apoptosis. Reporter assay showed that the E2F-1 site in FHIT 5' region was involved in the down-stream transcription after exogenous E2F-1 introduction. Chromatin immunoprecipitation detected exogenous E2F-1 binding to the recognition site in FHIT 5' region. The data suggest that E2F-1 overexpression plays a role in suppression of tumor, at least in part trough transcriptional regulation of FHIT and relevant activation of WWOX. (C) 2004 Elsevier Inc. All rights reserved.