Document Detail


Expression of Epstein-Barr virus-encoded LMP1 and hTERT extends the life span and immortalizes primary cultures of nasopharyngeal epithelial cells.
MedLine Citation:
PMID:  20827769     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cell immortalization is regarded as an early and pre-requisite step in tumor development. Defining the specific genetic events involved in cell immortalization may provide insights into the early events of carcinogenesis. Nasopharyngeal carcinoma is common among the Southern Chinese population. Epstein-Barr virus (EBV) infection is associated closely with nasopharyngeal carcinoma. The involvement of LMP1 (an EBV-encoded oncogene) has been implicated in the pathogenesis of nasopharyngeal carcinoma. In this study, LMP1 expression, in combination with ectopic expression of hTERT (catalytic unit of human telomerase), was shown to extend the life span of primary cultures of nasopharyngeal epithelial cells and facilitate the immortalization of one of the cell lines (NP446). This is the first report on the successful immortalization of nasopharyngeal epithelial cells involving LMP1. The events associated with the immortalization of nasopharyngeal epithelial cells by LMP1/hTERT were characterized. Expression of c-Myc, Bmi-1, and Id-1 were upregulated at an early stage of immortalization. At a later stage of immortalization, downregulation of p21 and p16 expression were observed. Upregulation of EGFR expression and activation of MAPK signaling pathway were observed in LMP1/hTERT-immortalized nasopharyngeal epithelial cells. The LMP1/hTERT-immortalized NP446 cells were non-tumorigenic in immunosuppressed nude mice and retained anchorage-dependent growth, suggesting that additional events are required for tumorigenic transformation. The ability of the EBV-encoded LMP1, in the presence of hTERT expression, to extend the life span and immortalize primary cultures of nasopharyngeal epithelial cells supports the involvement of EBV infection and its viral products in the early stage of pathogenesis of nasopharyngeal carcinoma.
Authors:
Yim-Ling Yip; Chi-Man Tsang; Wen Deng; Pak-Yan Cheung; Yuesheng Jin; Annie Lai-Man Cheung; Maria Li Lung; Sai-Wah Tsao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of medical virology     Volume:  82     ISSN:  1096-9071     ISO Abbreviation:  J. Med. Virol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-09     Completed Date:  2010-12-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7705876     Medline TA:  J Med Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1711-23     Citation Subset:  IM    
Copyright Information:
(c) 2010 Wiley-Liss, Inc.
Affiliation:
Cancer Biology Laboratory, Li Ka Shing Faculty of Medicine, Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
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MeSH Terms
Descriptor/Qualifier:
Adult
Cell Transformation, Neoplastic*
Cells, Cultured
Epithelial Cells / cytology*
Female
Gene Expression Profiling
Gene Expression Regulation
Humans
Male
Nasopharynx / cytology*
Telomerase / biosynthesis*
Viral Matrix Proteins / biosynthesis*
Chemical
Reg. No./Substance:
0/EBV-associated membrane antigen, Epstein-Barr virus; 0/Viral Matrix Proteins; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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