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Expression of Epstein-Barr Virus-Encoded LMP1 and hTERT Extends the Life Span and Immortalizes Primary Cultures of Nasopharyngeal Epithelial Cells

Yip, Yim-Ling; Tsang, Chi-Man; Deng, Wen; Cheung, Pak-Yan; Jin, Yuesheng LU ; Cheung, Annie Lai-Man; Lung, Maria Li and Tsao, Sai-Wah (2010) In Journal of Medical Virology 82(10). p.1711-1723
Abstract
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... (More)
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. J. Med. Virol. 82:1711-1723, 2010. (C) 2010 Wiley-Liss, Inc. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
nasopharyngeal carcinoma, LMP1, EGFR, immortalization, telomerase
in
Journal of Medical Virology
volume
82
issue
10
pages
1711 - 1723
publisher
John Wiley & Sons
external identifiers
  • wos:000281081000013
  • scopus:77956601081
ISSN
1096-9071
DOI
10.1002/jmv.21875
language
English
LU publication?
yes
id
87df6ebe-cb0e-4fdb-bae8-8f8617ee14d8 (old id 1673684)
date added to LUP
2010-09-23 08:13:23
date last changed
2018-05-29 11:27:35
@article{87df6ebe-cb0e-4fdb-bae8-8f8617ee14d8,
  abstract     = {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. J. Med. Virol. 82:1711-1723, 2010. (C) 2010 Wiley-Liss, Inc.},
  author       = {Yip, Yim-Ling and Tsang, Chi-Man and Deng, Wen and Cheung, Pak-Yan and Jin, Yuesheng and Cheung, Annie Lai-Man and Lung, Maria Li and Tsao, Sai-Wah},
  issn         = {1096-9071},
  keyword      = {nasopharyngeal carcinoma,LMP1,EGFR,immortalization,telomerase},
  language     = {eng},
  number       = {10},
  pages        = {1711--1723},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Medical Virology},
  title        = {Expression of Epstein-Barr Virus-Encoded LMP1 and hTERT Extends the Life Span and Immortalizes Primary Cultures of Nasopharyngeal Epithelial Cells},
  url          = {http://dx.doi.org/10.1002/jmv.21875},
  volume       = {82},
  year         = {2010},
}