Kim Kwonseop, Oh Minsoo, Ki Hyunkyoung, Wang Tao, Bareiss Sonja, Fini M Elizabeth, Li Dawei, Lu Qun
Department of Anatomy and Cell Biology, The Brody School of Medicine, East Carolina University, 600 Moye Street, Greenville, NC 27834, USA.
Biochem Biophys Res Commun. 2008 May 2;369(2):414-20. doi: 10.1016/j.bbrc.2008.02.069. Epub 2008 Feb 25.
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 delta-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.
δ-连环蛋白在人类癌症中上调。然而,关于在癌症中调节δ-连环蛋白表达的潜在转录因子知之甚少。利用人类δ-连环蛋白报告系统,我们筛选了几种核信号调节剂,以测试它们是否能影响δ-连环蛋白的转录。在β-连环蛋白/淋巴样增强因子1(LEF-1)、Notch1和E2F1中,E2F1显著增加了δ-连环蛋白荧光素酶活性,而β-连环蛋白/LEF-1仅引起少量增加。视网膜母细胞瘤蛋白(Rb)抑制了E2F1诱导的δ-连环蛋白荧光素酶活性上调,但不与δ-连环蛋白相互作用。对4种不同前列腺癌细胞系进行的逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹分析表明,δ-连环蛋白表达的调控主要在转录水平。有趣的是,仅在表达丰富内源性δ-连环蛋白的人类癌细胞中观察到E2F1对δ-连环蛋白表达的影响。这些研究确定E2F1是δ-连环蛋白的正向转录调节因子,但进一步表明在具有最低内源性δ-连环蛋白表达的前列腺癌细胞中存在δ-连环蛋白的强负向调节因子。