Negative feedback regulation of IFN-gamma pathway by IFN regulatory   factor 2 in esophageal cancers

doi:10.1158/0008-5472.CAN-07-5021

CORC > 北京大学 > 生命科学学院

	Negative feedback regulation of IFN-gamma pathway by IFN regulatory factor 2 in esophageal cancers
	Wang, Yan ; Liu, Dongping ; Chen, Pingping ; Koeffler, H. Philip ; Tong, Xiangjun ; Xie, Dong
刊名	cancer research
	2008
关键词	INTERFERON-GAMMA FAS-LIGAND T-CELLS TRANSCRIPTIONAL ACTIVATION EOSINOPHILIC ESOPHAGITIS TUMOR-DEVELOPMENT GENE-EXPRESSION FACTOR (IRF)-1 CYTOCHROME-C FACTOR-I
DOI	10.1158/0008-5472.CAN-07-5021
英文摘要	IFN-gamma is an antitumor cytokine that inhibits cell proliferation and induces apoptosis after engagement with the IFN-gamma receptors (IFNGR) expressed on target cells, whereas IFN regulatory factor 2 (IRF-2) is able to block the effects of IFN-gamma by repressing transcription of IFN-gamma-induced genes. Thus far, few studies have explored the influences of IFN-gamma on human esophageal cancer cells. In the present study, therefore, we investigated in detail the functions of IFN-gamma in esophageal cancer cells. The results in clinical samples of human esophageal cancers showed that the level of IFN-gamma was increased in tumor tissues and positively correlated with tumor progression and IRF-2 expression, whereas the level of IFNGR1 was decreased and negatively correlated with tumor progression and IRF-2 expression. Consistently, in vitro experiments showed that low concentration of IFN-gamma induced the expression of IRF-2 with potential promotion of cell growth, and moreover, IRF-2 was able to suppress IFNGR1 transcription in human esophageal cancer cells by binding a specific motif in IFNGR1 promoter, which lowered the sensitivity of esophageal cancer cells to IFN-gamma. Taken together, our results disclosed a new IRF-2-mediated inhibitory mechanism for IFN-gamma-induced pathway in esophageal cancer cells: IFN-gamma induced IRF-2 upregulation, then up-regulated IRF-2 decreased endogenous IFNGR1 level, and finally, the loss of IFNGR1 turned to enhance the resistance of esophageal cancer cells to IFN-gamma. Accordingly, the results implied that IRF-2 might act as a mediator for the functions of IFN-gamma and IFNGR1 in human esophageal cancers.; Oncology; SCI(E); 21; ARTICLE; 4; 1136-1143; 68
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/401368]
专题	生命科学学院
推荐引用方式 GB/T 7714	Wang, Yan,Liu, Dongping,Chen, Pingping,et al. Negative feedback regulation of IFN-gamma pathway by IFN regulatory factor 2 in esophageal cancers[J]. cancer research,2008.
APA	Wang, Yan,Liu, Dongping,Chen, Pingping,Koeffler, H. Philip,Tong, Xiangjun,&Xie, Dong.(2008).Negative feedback regulation of IFN-gamma pathway by IFN regulatory factor 2 in esophageal cancers.cancer research.
MLA	Wang, Yan,et al."Negative feedback regulation of IFN-gamma pathway by IFN regulatory factor 2 in esophageal cancers".cancer research (2008).