Latent membrane protein-1 of Epstein-Barr virus inhibits cell growth and induces sensitivity to cisplatin in nasopharyngeal carcinoma cells
Latent membrane protein-1 of Epstein-Barr virus inhibits cell growth and induces sensitivity to cisplatin in nasopharyngeal carcinoma cells
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DOI：
10.1002/jmv.2112
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发表时间：
2002-01-01
影响因子：
12.7
通讯作者：
Tsao, SW
中科院分区：
文献类型：
--
作者：
Liu, Y;Wang, XH;Tsao, SW
鼻咽癌与EB病毒（Epstein-Barr virus，EBV）密切相关，EBV编码的潜伏膜蛋白-1（latent membrane protein-1，LMP 1）在肿瘤细胞中普遍表达。LMP 1已被证明参与调节B细胞中的细胞生长，但LMP 1在鼻咽癌细胞中表达的生物学特性尚不明确。在这项研究中，全长LMP 1基因导入到EBV阴性的鼻咽癌细胞系，CNE 2，并分离出5个LMP 1表达克隆。LMP 1的表达并没有赋予CNE 2细胞细胞生长优势;相反，它在体外和体内都诱导了生长抑制。此外，LMP 1转染的细胞对顺铂诱导的细胞死亡更敏感，与载体感染的对照克隆相比，对顺铂的敏感性增加了1.4-4.0倍。LMP 1对Bcl-2和Bax比例平衡的影响可能在诱导顺铂诱导的细胞死亡的易感性中起作用。这些结果表明，LMP 1没有赋予CNE 2细胞的生长优势，表明LMP 1的表达可能不是维持细胞生长在建立的细胞系的关键。或者，单独的LMP 1可能不足以促进鼻咽癌细胞生长，并且可能需要另外的致癌因子与LMP 1一起沿着来调节鼻咽癌的恶性性质。(C)2002 Wiley-Liss，Inc.
Nasopharyngeal carcinoma is closely associated with Epstein-Barr virus (EBV) and the EBV encoded latent membrane protein-1 expression (LMP1) is commonly found in the tumour cells. LMP1 has been shown to be involved in modulation of cell growth in B cells but the biological properties of LMP1 expression in nasopharyngeal carcinoma cells are less defined. In this study, a full length LMP1 gene was introduced into an EBV negative nasopharyngeal carcinoma cell line, CNE2, and five LMP1-expressing clones were isolated. Expression of LMP1 did not confer cell growth advantage in CNE2 cells; instead, it induced growth inhibition both in vitro and in vivo. In addition, the LMP1 transfected cells were more susceptible to cisplatin-induced cell death and showed 1.4-4.0-fold increased sensitivity to cisplatin compared to the vector infected control clones. The effect of LMP1 on the balance of Bcl-2 and Bax ratio may play a role in inducing susceptibility to cisplatin-induced cell death. These results demonstrated that LMP1 did not confer growth advantage in CNE2 cells, suggesting that expression of LMP1 may not be crucial in sustaining cell growth in established cell lines. Alternatively, LMP1 alone may not be sufficient to facilitate nasopharyngeal carcinoma cell growth and additional oncogenic factors may be needed along with LMP1 in modulating the malignant property of nasopharyngeal carcinoma. (C) 2002 Wiley-Liss, Inc.