File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Expression of epstein-barr virus-encoded LMP1 and hTERT extends the life span and immortalizes primary cultures of nasopharyngeal epithelial cells

TitleExpression of epstein-barr virus-encoded LMP1 and hTERT extends the life span and immortalizes primary cultures of nasopharyngeal epithelial cells
Authors
KeywordsEGFR
Immortalization
LMP1
Nasopharyngeal carcinoma
Telomerase
Issue Date2010
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/32763
Citation
Journal Of Medical Virology, 2010, v. 82 n. 10, p. 1711-1723 How to Cite?
AbstractCell 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. © 2010 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/124622
ISSN
2015 Impact Factor: 1.998
2015 SCImago Journal Rankings: 1.015
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong General Research FundHKU 7770/07M
AoE NPCAoE/M-06/08
University of Hong Kong
CRCG Grant200807176131
Funding Information:

Grant sponsor: Hong Kong General Research Fund; Grant number: HKU 7770/07M; Grant sponsor: AoE NPC; Grant number: AoE/M-06/08; Grant sponsor: University of Hong Kong CRCG Grant; Grant sponsor: CRCG Grant; Grant number: 200807176131.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorYip, YLen_HK
dc.contributor.authorTsang, CMen_HK
dc.contributor.authorDeng, Wen_HK
dc.contributor.authorCheung, PYen_HK
dc.contributor.authorJin, Yen_HK
dc.contributor.authorCheung, ALMen_HK
dc.contributor.authorLung, MLen_HK
dc.contributor.authorTsao, SWen_HK
dc.date.accessioned2010-10-31T10:44:46Z-
dc.date.available2010-10-31T10:44:46Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Medical Virology, 2010, v. 82 n. 10, p. 1711-1723en_HK
dc.identifier.issn0146-6615en_HK
dc.identifier.urihttp://hdl.handle.net/10722/124622-
dc.description.abstractCell 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. © 2010 Wiley-Liss, Inc.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/32763en_HK
dc.relation.ispartofJournal of Medical Virologyen_HK
dc.rightsJournal of Medical Virology. Copyright © John Wiley & Sons, Inc.-
dc.subjectEGFRen_HK
dc.subjectImmortalizationen_HK
dc.subjectLMP1en_HK
dc.subjectNasopharyngeal carcinomaen_HK
dc.subjectTelomeraseen_HK
dc.subject.meshCell Transformation, Neoplastic-
dc.subject.meshEpithelial Cells - cytology-
dc.subject.meshNasopharynx - cytology-
dc.subject.meshTelomerase - biosynthesis-
dc.subject.meshViral Matrix Proteins - biosynthesis-
dc.titleExpression of epstein-barr virus-encoded LMP1 and hTERT extends the life span and immortalizes primary cultures of nasopharyngeal epithelial cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0146-6615&volume=82&issue=10&spage=1711&epage=1723&date=2010&atitle=Expression+of+Epstein-Barr+virus-encoded+LMP1+and+hTERT+extends+the+life+span+and+immortalizes+primary+cultures+of+nasopharyngeal+epithelial+cellsen_HK
dc.identifier.emailDeng, W: wdeng@hkucc.hku.hken_HK
dc.identifier.emailCheung, ALM: lmcheung@hku.hken_HK
dc.identifier.emailLung, ML: mlilung@hku.hken_HK
dc.identifier.emailTsao, SW: gswtsao@hku.hken_HK
dc.identifier.authorityDeng, W=rp01640en_HK
dc.identifier.authorityCheung, ALM=rp00332en_HK
dc.identifier.authorityLung, ML=rp00300en_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/jmv.21875en_HK
dc.identifier.pmid20827769-
dc.identifier.scopuseid_2-s2.0-77956601081en_HK
dc.identifier.hkuros174414en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77956601081&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume82en_HK
dc.identifier.issue10en_HK
dc.identifier.spage1711en_HK
dc.identifier.epage1723en_HK
dc.identifier.isiWOS:000281081000013-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectCentre for Nasopharyngeal Carcinoma Research-
dc.identifier.scopusauthoridYip, YL=7005596403en_HK
dc.identifier.scopusauthoridTsang, CM=24831236400en_HK
dc.identifier.scopusauthoridDeng, W=7202223673en_HK
dc.identifier.scopusauthoridCheung, PY=14024149900en_HK
dc.identifier.scopusauthoridJin, Y=7404457413en_HK
dc.identifier.scopusauthoridCheung, ALM=7401806497en_HK
dc.identifier.scopusauthoridLung, ML=7006411788en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK
dc.identifier.citeulike7807043-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats