Inhibition of β-catenin-mediated transactivation by flavanone in AGS gastric cancer cells
Inhibition of β-catenin-mediated transactivation by flavanone in AGS gastric cancer cells
复制标题
DOI：
10.1016/j.bbrc.2005.03.242
复制
发表时间：
2005-06-17
影响因子：
3.1
通讯作者：
Yang, CH
中科院分区：
文献类型：
--
作者：
Park, CH;Hahm, ER;Yang, CH
近年来，越来越多的数据证明Writ通路激活可能是胃多步骤癌变的早期事件。我们检测了黄酮对AGS胃癌细胞β -catenin/Tef信号传导的影响。报告基因试验表明，黄酮能有效抑制β -catenin/Tcf信号传导。此外，在瞬时转染了不被GSK3 β磷酸化的β -catenin组成型突变基因的HEK293细胞中，黄酮对β -catenin/Tcf信号通路的抑制表明其抑制机制与β -catenin本身或下游组分有关。为了研究精确的抑制机制，我们进行了免疫荧光、Western blot和EMSA。因此，我们的数据显示，通过黄酮没有改变β -连环蛋白的分布和核β -连环蛋白的水平。此外，Tcf复合物与DNA的结合不受黄酮的影响。黄酮下调β -catenin/Tcf转录靶基因cyclinD1。这些数据表明，黄酮通过调节Tcf活性而不破坏β -catenin/Tcf复合物的形成，从而抑制β -catenin/Tcf应答基因的转录。(c) 2005爱思唯尔公司版权所有。
Recently, data which prove that Writ pathway activation may be an early event in multistep carcinogenesis in the stomach have been accumulating. We examined the effect of flavanone against beta-catenin/Tef signaling in AGS gastric cancer cells. Reporter gene assay showed that flavanone inhibited beta-catenin/Tcf signaling efficiently. In addition, the inhibition of beta-catenin/Tcf signaling by flavanone in HEK293 cells transiently transfected with constitutively mutant beta-catenin gene, whose product is not phosphorylated by GSK3 beta, indicates that its inhibitory mechanism was related to beta-catenin itself or downstream components. To investigate the precise inhibitory mechanism, we performed immunofluorescence, Western blot, and EMSA. As a result, our data revealed that there is no change of beta-catenin distribution and of nuclear beta-catenin levels through flavanone. In addition, the binding of Tcf complexes to DNA is not influenced by flavanone. The beta-catenin/Tcf transcriptional target gene cyclinD1 was downregulated by flavanone. These data suggest that flavanone inhibits the transcription of beta-catenin/Tcf responsive genes, by modulating Tcf activity without disrupting beta-catenin/Tcf complex formation. (c) 2005 Elsevier Inc. All rights reserved.