鼻咽癌组织中EB病毒LMP1与Fascin及磷酸化Stat3表达的相关性

Correlation of Epstein-Barr Virus-encoded Latent Membrane Protein 1(LMP1) to Fascin and Phosphorylated Stat3 in Nasopharyngeal Carcinoma

背景与目的:EB病毒潜伏膜蛋白1(latent membrane protein 1,LMP1)是一重要的癌基因。Fascin蛋白是一种能与F-肌动蛋白结合的细胞骨架蛋白,参与细胞的迁移、粘附等功能。磷酸化的信号转导及转录激活因子3(phosphorylated signal transducer and activator of transcription 3,pStat3)是信号转导及转录激活因子(STATs)家族中与人类肿瘤发生发展密切相关的一种蛋白。本实验通过检测鼻咽癌及淋巴结转移癌中LMP1、Fascin和pStat3的表达,以探讨这些指标在鼻咽癌发生发展中的意义。方法:采用原位杂交和免疫组化法分别检测43例鼻咽癌组织(21例伴淋巴结转移;22例未伴淋巴结转移)及相应的21例癌转移淋巴结中EB病毒编码的非多聚腺苷酸RNA(EBV-encoded small RNA,EBER)的表达及LMP1、Fascin、pStat3、p53、Ki-67和Bcl-2的表达,并采用统计学分析上述各蛋白表达水平之间的相关性。采用Western blot检测转染LMP1表达质粒对鼻咽癌细胞中Fascin和pStat3表达的影响。结果:43例鼻咽癌组织及21例癌转移淋巴结中,EBER均呈阳性表达;43例鼻咽癌组织中,LMP1、Fascin、pStat3、p53、Ki-67、Bcl-2的阳性表达率分别为69.8%(30/43)、93.0%(40/43)、72.1%(31/43)、90.7%(39/43)、88.4%(38/43)、88.4%(38/43),LMP1的表达与其余5种指标的表达之间均具有明显的正相关(P<0.05)。21例鼻咽癌淋巴结转移组织中LMP1表达率为46.7%(10/21)。LMP1表达可明显提高鼻咽癌细胞中Fascin和pStat3的表达水平。结论:鼻咽癌组织及淋巴结转移癌组织中LMP1均有较高的表达率。鼻咽癌组织中LMP1表达与Fascin和pStat3表达之间均存在正相关。LMP1表达可明显上调鼻咽癌细胞中Fascin和pStat3的表达水平。LMP1的表达与癌细胞的增殖指数密切相关。

BACKGROUND ＆ OBJECTIVE= Latent membrane protein 1 （LMP1） of Epstein-Barr （EB） virus is an important oncogene. Fascin is an actin cross-linking protein involved in cell migration and adhesion. Phosphorylated signal transducer and activator of transcription 3 （pStat3） is a member of STATs family, which is closely related to tumorigenesis. This study was to investigate expressions of LMP1, Fascin and pStat3 in nasopharyngeal carcinoma （NPC） tissues and lymph node metastases of NPC, thus to explore their correlations to the initiation and progression of NPC. METHODS. Expressions of EBV-encoded small RNA （EBER）, LMP1, Fascin, pStat3, p53, Ki-67 and Bcl-2 were detected in 43 NPC tissues （21 with and 22 without lymph node metastases） and 21 corresponding lymph node metastases using in situ hybridization or immunohistochemistry （IHC）. Data were statistically analyzed. Expressions of pStat3 and Fascin were measured in the NPC cell line CNE1 transfected with LMPl-expressing plasmid using Western blot. RESULTS= Positive EBER expression was detected in all 43 NPC tissues and 21 lymph node metastases in NPC. The expression rates of LMP1, Fascin, pStat3, p53, Ki-67, and Bcl-2 were 69.8%（30/43）, 93.0% （40/43）, 72.1% （31/43）, 90.7% （39/43）, 88.4% （38/43） and 88.4% （38/43）in 43 NPC tissues, respectively. LMP1 expression was positively correlated with the expression level of Fascin, pStat3, p53, Ki-67 and Bcl-2 in 43 NPC cases（P〈0.05）. LMP1 was found in 10 out of 21 （46.7%） lymph node metastases in NPC. In addition, LMP1 expression dramatically increased pStat3 and Fascin in CNE1 cells. CONCLUSIONS. LMP1 is expressed in lymph node metastatases in NPC. The expression of LMP1 is positively correlated with Fascin, pStat3 and the proliferation index of tumor cells. Moreover, LMP1 up-regulates pStat3 and Fascin in NPC cells.