EB病毒潜伏膜蛋白1介导的上皮-间质转化增强鼻咽癌的转移潜能
Epstein-Barr virus-latent membrane protein 1-mediated epithelial-mesenchymal transition enhances the metastatic potential of nasopharyngeal carcinoma
摘 要
目的:探讨EB病毒潜伏膜蛋白1(latent membrane protein 1,LMP1)和p38在鼻咽癌上皮-间质转化(epithelial -mesenchymal transition,EMT)中的调控作用,分析其介导的EMT与肿瘤转移的关系。方法:采用免疫组织/细胞化学法、RT-PCR和蛋白质印迹法等检测鼻咽癌组织及鼻咽癌细胞中E-cadherin、vimentin、LMP1和p38的表达,Transwell实验检测鼻咽癌细胞的侵袭和运动能力。结果:E-cadherin在鼻咽癌和鼻咽癌颈部转移淋巴结组织中的阳性表达率有降低趋势(P<0.01),而vimentin和LMP1的阳性表达率有升高趋势(P<0.001),p38的阳性表达率差异则无统计学意义(P>0.05)。鼻咽癌组织中LMP1与E-cadherin的表达呈负相关(P<0.05);鼻咽癌颈部转移淋巴结组织中LMP1与E-cadherin的表达无相关性(P>0.05),而与vimentin的表达呈正相关(P<0.05)。E-cadherin mRNA和蛋白在CNE1-GL和CNE2Z细胞中的表达减弱,而vimentin mRNA和蛋白的表达增强。LMP1蛋白在CNE1-GL和CNE2Z细胞中高表达,p38蛋白则在CNE1-GL中高表达。Transwell实验证明,LMP1能够促进鼻咽癌细胞的运动和侵袭能力(P<0.001)。结论:LMP1可诱导鼻咽癌EMT,增强鼻咽癌的转移潜能。
EB病毒潜伏膜蛋白1
p38
上皮-间质转化
转移
Nasopharyngeal neoplasms
Epstein-Barr virus-latent membrane protein 1
p38
epithelial-mesenchymal transition
Metastasis
Abstract
Objective:To investigate the effects of Epstein-Barr virus-latent membrane protein 1(LMP1) and p38 mediating epithelial-mesenchymal transition of nasopharyngeal carcinoma(NPC),and to elucidate its relationship with tumor metastasis.Methods:The expression levels of E-cadherin,vimentin,LMP1 and p38 in NPC tissues and cell lines were detected by immunohistochemistry,immunocytochemistry,RT-PCR and Western blotting.The invasion and migration abilities of NPC cell lines were examined by Transwell assay.Results:The positive expression rates of E-cadherin in different NPC tissues and lymph node metastases were decreased(P<0.01),whereas the positive expression rates of vimentin and LMP1 were increased(P<0.001).The difference in the positive expression rate of p38 was not statistically significant(P>0.05).The expression of LMP1 was negatively associated with the expression of E-cadherin in NPC tissues(P<0.05).In cervical lymph node metastasis,the expression of LMP1,which had no association with the expression of E-cadherin(P>0.05),was associated with the expression of vimentin(P<0.05).The expressions of E-cadherin mRNA and protein were suppressed in CNE1-GL and CNE2Z cells,whereas the expressions of vimentin mRNA and protein were increased.The expression level of LMP1 protein was high in CNE1-GL and CNE2Z cells,and the expression level of p38 protein was high in CNE1-GL cells.Transwell assay showed that LMP1 could promote the migration and invasion abilities of NPC cells(P<0.001).Conclusion:LMP1 can induce EMT and enhance the metastatic potential of nasopharyngeal carcinoma.
中图分类号 R739.63 DOI 10.3781/j.issn.1000-7431.2011.07.010
所属栏目 临床研究
基金项目 广东省教育厅重点学科建设基金资助项目(编号:GX0305);湛江市科技计划项目(编号:2007C05017);广东医学院2007年度科研项目(编号:M2007008)
收稿日期 2010/10/25
修改稿日期 2011/1/17
网络出版日期
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引用该论文: LI Rong,JING Min,LI Xiao-bing,ZHU Shao-ping,HUANG Pei-chun. Epstein-Barr virus-latent membrane protein 1-mediated epithelial-mesenchymal transition enhances the metastatic potential of nasopharyngeal carcinoma[J]. Tumor, 2011, 31(7): 627～632
李蓉,敬敏,黎小兵,朱少平,黄培春. EB病毒潜伏膜蛋白1介导的上皮-间质转化增强鼻咽癌的转移潜能[J]. 肿瘤, 2011, 31(7): 627～632
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参考文献
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【2】YOSHIZAKI T, WAKISAKA N, PAGANO J S. Epstein-Barr virus, invasion and metastasis[M]. Norfolk (United Kingdom):Caister Academic Press, 2005:171-196.
【3】申志华, 陈小毅, 陈 锦, 等. EBV-LMP1上调Ezrin表达对鼻咽癌细胞转移潜能的影响[J]. 癌症, 2008, 27(2):165-169.
【4】申志华, 陈小毅, 陈 锦, 等. EBV-LMP1上调Ezrin表达对鼻咽癌细胞转移潜能的影响[J]. 癌症, 2008, 27(2):165-169.
【5】欧小波, 陈小毅, 吴民华, 等. EB病毒LMP1对人鼻咽癌细胞转移能力的影响[J]. 癌症, 2008, 27(8):803-808.
【6】欧小波, 陈小毅, 吴民华, 等. EB病毒LMP1对人鼻咽癌细胞转移能力的影响[J]. 癌症, 2008, 27(8):803-808.
【7】SMIT M A, PEEPER D S. Epithelial-mesenchymal transition and senescence:two cancer-related processes are crossing paths[J]. Aging, 2010, 2(10):735-741.
【8】SMIT M A, PEEPER D S. Epithelial-mesenchymal transition and senescence:two cancer-related processes are crossing paths[J]. Aging, 2010, 2(10):735-741.
【9】赵俊卿, 李云峰, 杨之斌. 肿瘤细胞发生细胞上皮-间质转变机制的研究[J]. 肿瘤, 2010, 30(10):890-893.
【10】赵俊卿, 李云峰, 杨之斌. 肿瘤细胞发生细胞上皮-间质转变机制的研究[J]. 肿瘤, 2010, 30(10):890-893.
【11】陈 燕, 陈小毅. EBV-LMP1对鼻咽癌细胞系CNE1细胞调亡的影响[J]. 癌症, 2002, 21(5):498-503.
【12】陈 燕, 陈小毅. EBV-LMP1对鼻咽癌细胞系CNE1细胞调亡的影响[J]. 癌症, 2002, 21(5):498-503.
【13】CHEW M M, GAN S Y, KHOO A S, et al. Interleukins, laminin and epstein-barr virus latent membrane protein 1 (EBV LMP1) promote metastatic phenotype in nasopharyngeal carcinoma[J]. BMC Cancer, 2010, 10:574.
【14】CHEW M M, GAN S Y, KHOO A S, et al. Interleukins, laminin and epstein-barr virus latent membrane protein 1 (EBV LMP1) promote metastatic phenotype in nasopharyngeal carcinoma[J]. BMC Cancer, 2010, 10:574.
【15】LI G, WU Z, PENG Y, et al. MicroRNA-10b induced by Epstein-Barr virus-encoded latent membrane protein-1 promotes the metastasis of human nasopharyngeal carcinoma cells[J]. Cancer Lett, 2010, 299(1):29-36.
【16】LI G, WU Z, PENG Y, et al. MicroRNA-10b induced by Epstein-Barr virus-encoded latent membrane protein-1 promotes the metastasis of human nasopharyngeal carcinoma cells[J]. Cancer Lett, 2010, 299(1):29-36.
【17】HO C H, CHEN C L, LI W Y, et al. Decoy receptor 3, upregulated by Epstein-Barr virus latent membrane protein 1, enhances nasopharyngeal carcinoma cell migration and invasion[J]. Carcinogenesis, 2009, 30(8):1443-1451.
【18】HO C H, CHEN C L, LI W Y, et al. Decoy receptor 3, upregulated by Epstein-Barr virus latent membrane protein 1, enhances nasopharyngeal carcinoma cell migration and invasion[J]. Carcinogenesis, 2009, 30(8):1443-1451.
【19】HORIKAWA T, YANG J, KONDO S, et al. Twist and epithelial-mesenchymal transition are induced by the EBV oncoprotein latent membrane protein 1 and are associated with metastatic nasopharyngeal carcinoma[J]. Cancer Res, 2007, 67(5):1970-1978.
【20】HORIKAWA T, YANG J, KONDO S, et al. Twist and epithelial-mesenchymal transition are induced by the EBV oncoprotein latent membrane protein 1 and are associated with metastatic nasopharyngeal carcinoma[J]. Cancer Res, 2007, 67(5):1970-1978.
【21】MATSUO N, SHIRAHA H, FUJIKAWA T, et al. Twist expression promotes migration and invasion in hepatocellular carcinoma[J]. BMC Cancer, 2009, 9:240.
【22】MATSUO N, SHIRAHA H, FUJIKAWA T, et al. Twist expression promotes migration and invasion in hepatocellular carcinoma[J]. BMC Cancer, 2009, 9:240.
【23】JETHWA P, NAQVI M, HARDY R G, et al. Overexpression of Slug is associated with malignant progression of esophageal adenocarcinoma[J]. World J Gastroenterol, 2008, 14(7):1044-1052.
【24】JETHWA P, NAQVI M, HARDY R G, et al. Overexpression of Slug is associated with malignant progression of esophageal adenocarcinoma[J]. World J Gastroenterol, 2008, 14(7):1044-1052.
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