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潜伏膜蛋白1 对鼻咽癌细胞CNE1 中端粒酶的 激活作用及相关调控机制

Activation of LMP1 to Telomerase in Human Nasopharyngeal Cell Line, CNE1 and Related Regulation Mechanisms

  • 摘要: 目的 探讨LMP1 对鼻咽癌上皮样细胞系CNE1 (nasopharyngeal carcinoma epithelioid cell lines, CNE ) 中端粒酶活性的影响及相关调控机制。方法 分别采用SP 法、RT2PCR 法和PCR2ELISA 法检测鼻咽癌细胞CNE1 、CNE1GL (转染了目的基因质粒PAT2GFP2LMP1 的CNE1 细胞株) 和CNE22Z 中LMP1 、NF2κB、c2myc 和hTERT 的表达、hTERT mRNA 水平和端粒酶活性。结果 (1) CNE1GL 与CNE1 细胞相比,LMP1 、NF2κB、c2myc、hTERT 的表达水平均高于CNE1 细胞中各指标的表达,差异有统计学意义( P <0. 01) 。CNE22Z和CNE1GL 、CNE1 相比,细胞中各指标的表达水平均最高( P < 0. 01 或P < 0. 05) 。CNE1GL 细胞中,LMP1 与NF2κB、NF2κB 与c2myc 及LMP1 与c2myc 的表达之间均呈显著正相关( P <0. 01或P < 0. 05) 。(2) hTERT mRNA 水平在CNE1GL 细胞明显高于CNE1 细胞,差异有统计学意义( P <0. 01) ;在三种细胞中,CNE22Z细胞中hTERT mRNA 水平最高( P < 0. 01) 。(3) CNE1GL 细胞中的端粒酶活性明显高于CNE1 细胞,差异有统计学意义( P < 0. 05) ;CNE1GL 细胞中的端粒酶活性略低于CNE22Z 细胞( P > 0. 05) ;CNE22Z细胞中的端粒酶活性明显高于CNE1 细胞( P < 0. 01) 。结论 在CNE1GL 细胞中,LMP1 通过激活hTERT 转录而激活端粒酶。此调控过程可能和NF2κB 激活,NF2κB 进而上调c2myc 表达水平,c2myc 提高hTERT 转录水平有关。LMP1 激活端粒酶可能是鼻咽癌癌变过程中的重要事件。

     

    Abstract: Objective  To explore the influence to telomerase activity and related regulation mechanisms of LMP1 in a NPC cell line, CNE1. Methods  The expressions of LMP1, NF2κB, c2myc and hTERT, the lev2 el of hTERT mRNA and the telomerase activity were respectively detected by SP, RT2PCR and PCR2 EL ISA methods in NPC cell line CNE1, CNE1 GL (CNE1 t ransfected with an eukaryotic plasmid, PAT2 GFP2LMP1) and CNE22Z. Results  (1) The expressions of LMP1, NF2κB, c2myc and hTERT in CNE1 GL is higher than those in CNE1 ( P < 0. 01) . Among three types of cells, the expressions of LMP1, NF2κB and c2myc and hTERT in CNE22Z was highest ( P < 0. 01 or P < 0. 05) . Pearson correlation analysis showed that the expressions between LMP1 and NF2κB, NF2κB and c2myc, LMP1 and c2myc in CNE1 GL were significantly correlated ( P < 0. 01 or P < 0. 05) . ( 2) The hTERT mRNA level in CNE1 GL was higher than that in CNE1, the difference was statistial significant ( P < 0. 01) ; the hTERT mRNA level in CNE22Z was highest in three types of cells ( P < 0. 01) . (3) The telomerase activity in CNE1 GL was high2 er than that in CNE1, the difference was statistical significant ( P < 0. 05 ) ; the telomerase activity in CNE1 GL was a little lower than that in CNE22Z( P > 0. 05) ; the telomerase activity in CNE22Z was high2 er than that in CNE1 ( P < 0. 01) . Conclusion  LMP1 activates telomerase by activating hTERT t ranscrip2 tion. This process is possibly related to NF2κB activation by LMP1, upregulating the expression of c2myc by NF2κB and improving t ranscription level of hTERT by c2myc in CNE1 GL. Telomerase activation by LMP1 may be an important occurrence in the stage of tumorigeness of NPC.

     

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