期刊文献+

XAF1 mediates apoptosis through an extracellular signal-regulated kinase pathway in colon cancer 预览

XAF1 mediates apoptosis through an extracellular signal-regulated kinase pathway in colon cancer
在线阅读 下载PDF
分享 导出
摘要 Background:XIAP-associated factor 1(XAF1)negatively regulates the function of the X-linked inhibitor of apoptosis protein(XIAP),a member of the IAP family that exerts antiapoptotic effects.The extracellular signal-regulated kinase(ERK)pathway is thought to increase cell proliferation and to protect cells from apoptosis.The aim of the study was to investigate the correlation between the ERK1/2 signaling pathway and XAF1 in colon cancer.Methods:Four human colon cancer cell lines,HCT1116 and Lovo(wildtype p53),DLD1 and SW1116(mutant p53),were used.Lovo stable transfectants with XAF1 sense and antisense were established.The effects of dominant-negative MEK1(DN-MEK1)and MEK-specific inhibitor U0126 on the ERK signaling pathway and expression of XAF1 and XIAP proteins were determined.The transcription activity of core XAF1 promoter was assessed by dual luciferase reporter assay.Cell proliferation was measured by MTT assay.Apoptosis was determined by Hoechst 33258 staining.Results:U0126 increased the expression of XAF1 in a time-and dose-dependent manner.A similar result was obtained in cells transfected with DN-MEK1 treatment.Conversely,the expression of XIAP was down-regulated.Activity of the putative promoter of the XAF1 gene was significantly increased by U0126 treatment and DN-MEK1 transient transfection.rhEGF-stimulated phosphorylation of ERK appeared to have little or no effect on XAF1 expression.Overexpression of XAF1 was more sensitive to U0126-induced apoptosis,whereas down-regulation of XAF1 by antisense reversed U0126-induced inhibition of cell proliferation.Conclusions:XAF1 expression was up-regulated by inhibition of the ERK1/2 pathway through transcriptional regulation,which required de novo protein synthesis.The results suggest that XAF1 mediates apoptosis induced by the ERK1/2 pathway in colon cancer. Background: XIAP-associated factor 1 (XAF1) negatively regulates the function of the X-linked inhibitor of apoptosis protein (XIAP) , a member of the IAP family that exerts antiapoptotic effects. The extracellular signal-regulated kinase (ERK) pathway is thought to in- crease cell proliferation and to protect cells from apoptosis. The aim of the study was to investigate the correlation between the ERK1/2 signaling pathway and XAF1 in colon cancer. Methods: Four human colon cancer cell lines, HCT1116 and Lovo (wildtype p53 ) , DLDI and SW1116 (mutant 053 ) . were used. Lovo stable transfectants with XAF1 sense and antisense were established.
作者 俞丽芬 王继德 邹冰 王振宇 YU LF, WANG J, ZOU B, et al (Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China)
出处 《上海交通大学学报:医学版》 CAS CSCD 北大核心 2007年第5期 541,共1页 Journal of Shanghai Jiaotong University:Medical Science
基金 Shanghai Medical Key Discipline Construction Foundation(05 - Ⅲ -005 -017).
关键词 细胞凋亡 结肠癌 胞外信号传导激酶 路径 XIAP XAF1 细胞因子 抑制剂 extracellular signal-regulated kinase inhibitors of apoptosis proteins X chromosome-linked IAP XIAP-associated factor 1
作者简介 Correspondence author : Wong BC (王振宇 )
  • 相关文献
投稿分析

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部 意见反馈