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为了探讨EB病毒潜伏膜蛋白 1(LMP1)的致瘤机制 ,对鼻咽癌细胞中LMP1通过核转录因子κB(NFκB)介导的信号传导途径在鼻咽癌变中的意义进行了研究。利用LMP1受四环素衍生物强力霉素诱导表达的鼻咽癌细胞Tet on LMP1HNE2 ,通过NFκB报道基因分析法、凝胶迁移率分析 (EMSA)及细胞集落形成率等方法 ,结合硫代磷酸反义寡核苷酸阻断技术 ,证实LMP1增强鼻咽癌细胞NFκB的DNA结合活性和反式激活活性 ,这种增强的活性可被LMP1及NFκBp6 5硫代磷酸反义寡核苷酸阻断 ,而NFκBp5 0仅阻断DNA结合活性 ,对反式激活活性无影响。同时 ,LMP1及NFκBp6 5硫代磷酸反义寡核苷酸可部分逆转鼻咽癌细胞的恶性表型 ,而反义 p5 0这种效应不显著。这些结果表明 ,LMP1在鼻咽癌中通过NFκB信号传导途径可能参与了鼻咽癌变 ,NFκBp6 5可能是主要的效应者。
In order to explore the mechanism of tumorigenicity of Epstein-Barr virus latent membrane protein 1 (LMP1), the role of LMP1 in nasopharyngeal carcinogenesis by nasal nuclear factor-κB (NFκB) -mediated signaling pathway was studied in nasopharyngeal carcinoma cells. Tet LMP1HNE2, a nasopharyngeal carcinoma cell line induced by tetracycline and doxycycline, was used to detect the expression of Tet-LMP1HNE2 by NFκB reporter gene assay, EMSA and cell colony forming rate Nucleotide blocking technology confirmed that LMP1 enhances the DNA binding activity and transactivation activity of NFκB in nasopharyngeal carcinoma cells. This enhanced activity can be blocked by LMP1 and NFκBp65 phosphorothioate antisense oligonucleotides, while NFκBp5 0 blocks DNA binding activity only and has no effect on transactivation activity. At the same time, LMP1 and NFκBp6 5 phosphorothioate antisense oligonucleotides partially reversed the malignant phenotype of nasopharyngeal carcinoma cells, while the effect of antisense p5 0 was not significant. These results indicate that LMP1 may be involved in NPC carcinogenesis through NFκB signaling pathway in NPC, and NFκBp65 may be the main effect.