Epstein-Barr virus encoded latent membrane protein 1 regulates mTOR signaling pathway genes which predict poor prognosis of nasopharyngeal carcinoma

Journal of Translational Medicine

Research

Chun-Fang Hu¹  Yi-Xin Zeng²  Xiao-Feng Zhu²  Qiong Shao³  Jing-Hui Hou³  Li-Xu Yan³  Jian-Yong Shao⁴  Jing Chen⁵ 

[1] Institute of Cancer Studies, University of Birmingham, B15 2TT, Birmingham, UK, UK;State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, China;Department of Experiment Research, Sun Yat-Sen University Cancer Center, Guangzhou, China;State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, China;Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China;State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, China;Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China;Department of Experiment Research, Sun Yat-Sen University Cancer Center, Guangzhou, China;State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, China;Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China;Department of Microbiolgy, Tumor and Cell Biology, Karolinska Institutet, Box 280, SE-17177, Stockholm, Sweden;

关键词: Latent Membrane Protein;    mTOR Signaling Pathway;    LMP1 Expression;    Regulate mTOR Signaling;    Cell Line HONE1;   

DOI  :  10.1186/1479-5876-8-30

 received in 2009-11-05, accepted in 2010-03-26,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe oncoprotein Epstain-Barr Virus (EBV)-encoded latent membrane protein1 (LMP1) modulates the pathological effects of the NF-κB, AP-1 and JAK/STAT pathways in nasopharyngeal carcinoma (NPC).MethodsMicroarray analysis was performed on the NPC cell line HONE1 stably transfected with a LMP1-expression plasmid or an empty vector. Based on assigned pathways analyzed using the KEGG database, the mTOR signaling pathway was selected for verification by quantitative RT-PCR. Western blot, RNA interference and immunofluorescence were used to determine the relationship between LMP1 and mTOR signing pathway genes, and their clinical significance to NPC.ResultsOur studies revealed that overexpression of LMP1 upregulated the mTOR signaling pathway, possibly through phosphorylation of AKT/mTOR/P70S6K/4EBP1 in the NPC cell lines HONE1 and 6-10B. Knockdown of LMP1 reduced expression of p-mTOR and p-4EBP1 in EBV-positive NPC cell line C666-1. In addition, LMP1 expression closely correlated with expression of p-mTOR, p-P70S6K and p-4EBP1 in NPC tumors. Expression of p-P70S6K, p-4EBP1 and LMP1, but not p-mTOR, significantly correlated with overall survival of NPC patients. However, only LMP1 was an independent prognostic factor.ConclusionsThese results suggest that the mTOR signaling pathway is regulated by LMP1 expression in NPC. LMP1 and the genes in the mTOR pathway such as p-P70S6K and p-4EBP1 may be potential prognostic biomarkers.

【 授权许可】

Unknown   
© Chen et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.