State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, China.
J Transl Med. 2010 Mar 26;8:30. doi: 10.1186/1479-5876-8-30.
The oncoprotein Epstain-Barr Virus (EBV)-encoded latent membrane protein1 (LMP1) modulates the pathological effects of the NF-kappaB, AP-1 and JAK/STAT pathways in nasopharyngeal carcinoma (NPC).
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.
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.
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.
致癌蛋白 Epstein-Barr 病毒（EBV）编码的潜伏膜蛋白 1（LMP1）调节鼻咽癌（NPC）中 NF-kappaB、AP-1 和 JAK/STAT 通路的病理效应。
对稳定转染 LMP1 表达质粒或空载体的 NPC 细胞系 HONE1 进行微阵列分析。根据 KEGG 数据库分析的指定途径，选择 mTOR 信号通路通过定量 RT-PCR 进行验证。Western blot、RNA 干扰和免疫荧光用于确定 LMP1 与 mTOR 信号通路基因之间的关系及其对 NPC 的临床意义。
我们的研究表明，LMP1 的过表达上调了 mTOR 信号通路，可能通过 NPC 细胞系 HONE1 和 6-10B 中的 AKT/mTOR/P70S6K/4EBP1 磷酸化实现。EBV 阳性 NPC 细胞系 C666-1 中 LMP1 的敲低降低了 p-mTOR 和 p-4EBP1 的表达。此外，LMP1 的表达与 NPC 肿瘤中 p-mTOR、p-P70S6K 和 p-4EBP1 的表达密切相关。p-P70S6K、p-4EBP1 和 LMP1 的表达，而不是 p-mTOR，与 NPC 患者的总生存率显著相关。然而，只有 LMP1 是独立的预后因素。
这些结果表明 mTOR 信号通路在 NPC 中受 LMP1 表达的调节。LMP1 及其在 mTOR 通路中的基因，如 p-P70S6K 和 p-4EBP1，可能是潜在的预后生物标志物。
