Epstein-Barr virus encoded latent membrane protein 1 regulates mTOR signaling pathway genes which predict poor prognosis of nasopharyngeal carcinom | Chen et al. Journal of Translational Medicine 2010 8 30 http content 8Z1 30 RESEARCH Open Access Epstein-Barr virus encoded latent membrane protein 1 regulates mTOR signaling pathway genes which predict poor prognosis of nasopharyngeal carcinoma Jing Chen 1 2 3 Chun-Fang Hu4 Jing-Hui Hou1 2 Qiong Shao1 2 Li-Xu Yan1 2 Xiao-Feng Zhu1 5 Yi-Xin Zeng1 5 and Jian-Yong Shao 1 2 5 Abstract Background The oncoprotein Epstain-Barr Virus EBV -encoded latent membrane protein1 LMP1 modulates the pathological effects of the NF-kB AP-1 and JAK STAT pathways in nasopharyngeal carcinoma NPC . Methods Microarray 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. Results Our 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. Conclusions These 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. Background Nasopharyngeal carcinoma NPC is a unique cancer of the head and neck that has a high incidence in Southern China where it is .
