Establishment of two immortalized nasopharyngeal epithelial cell lines using SV40 large T and HPV16E6/E7 viral oncogenes

Establishment of two immortalized nasopharyngeal epithelial cell lines using SV40 large T and HPV16E6/E7 viral oncogenes
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DOI:
10.1016/s0167-4889(02)00208-2
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发表时间:
2002-06-12
影响因子:
5.1
通讯作者:
Huang, DP
Huang, DP
中科院分区:
生物学2区
文献类型:
--
作者:
Tsao, SW;Wang, XH;Huang, DP

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鼻咽癌是东南亚地区,尤其是中国南方的常见肿瘤。这种疾病最显著的特征之一是它与EB病毒(EBV)的密切关系。然而,到目前为止,没有直接的研究参与的作用,EB病毒在鼻咽癌的肿瘤发生的机制,主要是由于缺乏一个实验模型。关于EBV和NPC之间的关联的可用假设是从非鼻咽上皮细胞系统如人角质形成细胞或小鼠上皮细胞产生的,其可能不能真实地代表鼻咽上皮(NP)细胞的生物学特性。本研究利用SV 40 T和HPV 16 E6/E7两种癌基因建立了两种永生化NP细胞系NP 69 SV 40 T和NP 39 E6/E7。我们发现,NP 60 SV 40 T和NP 39 E6/E7细胞系不仅保持了正常NP细胞的许多特征(即角蛋白谱和对TGF β抑制的响应),而且对EBV编码基因之一LMP 1高度响应。比较基因组杂交(CGH)分析表明,这两个细胞系含有多种遗传变异,其中一些已被描述在鼻咽癌。永生化NP细胞系是非致瘤性的,并表现出一种生长依赖性。这些细胞系为研究鼻咽癌的发生机制提供了一个可能的细胞模型系统。(C)2002 Elsevier Science B.V保留所有权利。
Nasopharytigeal carcinoma (NPC) is a common cancer in Southeast Asia, especially in southern China. One of the most striking features of this disease is its close relationship with Epstein-Barr Virus (EBV). However, to date there is no direct study on the mechanisms involved in the role of EBV in the tumorigenesis of NPC, largely due to lack of an experimental model. Available hypotheses on the association between EBV and NPC are generated from non-nasopharyngeal epithelial cell systems such as human keratinocytes or mouse epithelial cells, which may not truly represent the biological properties of nasopharyngeal epithelial (NP) cells. In this study, we report the establishment of two immortalized NP cell lines, NP69SV40T and NP39E6/E7, using SV40T and HPV16E6/E7 oncogenes. We found that NP60SV40T and NP39E6/E7 cell lines not only maintained many characteristics of normal NP cells (i.e. keratin profile and responsive to TGFbeta inhibition) but also highly responsive to one of the EBV encoded genes, LMP1. Comparative genome hybridization (CGH) analysis showed that these two cell lines contained multiple genetic alterations, some of which have been described in NPC. The immortalized NP cell lines are nontumorigenic and exhibit an chorage-dependent growth. These cell lines may provide a possible cell model system for studying the mechanisms involved in the tumorigenesis of NPC. (C) 2002 Elsevier Science B.V All rights reserved.