Identification of E2F1 as a positive transcriptional regulator for δ-catenin
Identification of E2F1 as a positive transcriptional regulator for δ-catenin
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DOI：
10.1016/j.bbrc.2008.02.069
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发表时间：
2008-05-02
影响因子：
3.1
通讯作者：
Lu, Qun
中科院分区：
文献类型：
--
作者：
Kim, Kwonseop;Oh, Minsoo;Lu, Qun
δ-连环蛋白在人癌中上调。然而，很少有人知道的潜在的转录因子，调节δ-连环蛋白在癌症中的表达。使用人类δ-连环蛋白报告系统，我们筛选了几种核信号调节剂，以测试它们是否可以影响δ-连环蛋白转录。在β-连环蛋白/LEF-1、Notch 1和E2 F1中，E2 F1显著增加5-连环蛋白-荧光素酶活性，而β-连环蛋白/LEF-1仅诱导少量增加。Rb抑制E2 F1诱导的δ-连环蛋白-荧光素酶活性的上调，但不与δ-连环蛋白相互作用。在4种不同的前列腺癌细胞系中的RT-PCR和Western印迹分析显示，δ-连环蛋白表达的调节主要在转录水平上控制。有趣的是，E2 F1对δ-连环蛋白表达的影响仅在表达丰富的内源性δ-连环蛋白的人癌细胞中观察到。这些研究将E2 F1鉴定为δ-连环蛋白的正转录调节因子，但进一步表明在具有最小内源性δ-连环蛋白表达的前列腺癌细胞中存在δ-连环蛋白的强负调节因子。(c)2008年爱思唯尔公司All rights reserved.
delta-Catenin is upregulated in human carcinomas. However, little is known about the potential transcriptional factors that regulate delta-catenin expression in cancer. Using a human delta-catenin reporter system, we have screened several nuclear signaling modulators to test whether they can affect delta-catenin transcription. Among beta-catenin/LEF-1, Notch1, and E2F1, E2F1 dramatically increased 5-catenin-luciferase activities while beta-catenin/LEF-1 induced only a marginal increase. Rb suppressed the upregulation of delta-catenin-luciferase activities induced by E2F1 but did not interact with delta-catenin. RT-PCR and Western blot analyses in 4 different prostate cancer cell lines revealed that regulation of delta-catenin expression is controlled mainly at the transcriptional level. Interestingly, the effects of E2F1 on delta-catenin expression were observed only in human cancer cells expressing abundant endogenous delta-catenin. These studies identify E2F1 as a positive transcriptional regulator for delta-catenin, but further suggest the presence of strong negative regulator(s) for delta-catenin in prostate cancer cells with minimal endogenous delta-catenin expression. (c) 2008 Elsevier Inc. All rights reserved.