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Article: Stable expression of EBERs in immortalized nasopharyngeal epithelial cells confers resistance to apoptotic stress

TitleStable expression of EBERs in immortalized nasopharyngeal epithelial cells confers resistance to apoptotic stress
Authors
Issue Date2005
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0899-1987/
Citation
Molecular Carcinogenesis, 2005, v. 44 n. 2, p. 92-101 How to Cite?
AbstractEpstein-Barr virus (EBV) infection is closely associated with the development of nasopharyngeal carcinoma (NPC). The EBV-encoded RNAs (EBERs) are the most abundant EBV transcripts (about 107 copies per cell) in EBV infected cells. However, the cellular function of EBER expression, particularly in nasopharyngeal epithelial cells, remains poorly understood. EBERs acquire secondary structures analogous to double-stranded RNA (dsRNA) and may bind to the double-stranded RNA-dependent protein kinase (PKR) and interfere with its function. Activation of PKR involves autophosphorylation resulting in protein synthesis inhibition and cellular apoptosis. Induction of cellular apoptosis by activation of PKR may be an antiviral response adopted by virally infected cells. We have examined the functional properties of EBER expression in an immortalized nasopharyngeal epithelial cell line (NP69). Expression of EBERs was achieved by transfecting the NP69 cells with an EBER-expressing plasmid, pESK10. The EBER-expressing NP69 cells attained a higher growth rate compared to cells transfected with control plasmid (pcDNA3). However, the EBER-expressing NP69 cells did not form colonies in soft agar and were non-tumorigenic in nude mice. To investigate if EBERs may protect the nasopharyngeal epithelial cells from apoptotic insults, we treated the EBER-expressing NP69 cells with a dsRNA analogue, poly(l).poly(C) (plC), to activate PKR in cells and examined for their responses. Lower level of PKR phosphorylation and elevation of Bcl-2 were observed in EBER-expressing NP69 cells. In addition, other apoptotic markers including the cleaved forms of caspase-3 and poly(ADP)ribose polymerase (PARP) were found to be lower in EBER-expressing NP69 cells after treatment with plC. Lower phosphorylation levels of p38 MARK (mitogen-activated protein kinase) and c-jun were also observed in EBER-expressing NP cells. Our results suggest that EBER expression may confer an apoptotic-resistant phenotype in immortalized nasopharyngeal epithelial cells. © 2005 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/67785
ISSN
2015 Impact Factor: 4.722
2015 SCImago Journal Rankings: 1.393
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWong, HLen_HK
dc.contributor.authorWang, Xen_HK
dc.contributor.authorChang, RCCen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorFeng, Hen_HK
dc.contributor.authorWang, Qen_HK
dc.contributor.authorLo, KWen_HK
dc.contributor.authorHuang, DPen_HK
dc.contributor.authorYuen, PWen_HK
dc.contributor.authorTakada, Ken_HK
dc.contributor.authorWong, YCen_HK
dc.contributor.authorTsao, SWen_HK
dc.date.accessioned2010-09-06T05:58:14Z-
dc.date.available2010-09-06T05:58:14Z-
dc.date.issued2005en_HK
dc.identifier.citationMolecular Carcinogenesis, 2005, v. 44 n. 2, p. 92-101en_HK
dc.identifier.issn0899-1987en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67785-
dc.description.abstractEpstein-Barr virus (EBV) infection is closely associated with the development of nasopharyngeal carcinoma (NPC). The EBV-encoded RNAs (EBERs) are the most abundant EBV transcripts (about 107 copies per cell) in EBV infected cells. However, the cellular function of EBER expression, particularly in nasopharyngeal epithelial cells, remains poorly understood. EBERs acquire secondary structures analogous to double-stranded RNA (dsRNA) and may bind to the double-stranded RNA-dependent protein kinase (PKR) and interfere with its function. Activation of PKR involves autophosphorylation resulting in protein synthesis inhibition and cellular apoptosis. Induction of cellular apoptosis by activation of PKR may be an antiviral response adopted by virally infected cells. We have examined the functional properties of EBER expression in an immortalized nasopharyngeal epithelial cell line (NP69). Expression of EBERs was achieved by transfecting the NP69 cells with an EBER-expressing plasmid, pESK10. The EBER-expressing NP69 cells attained a higher growth rate compared to cells transfected with control plasmid (pcDNA3). However, the EBER-expressing NP69 cells did not form colonies in soft agar and were non-tumorigenic in nude mice. To investigate if EBERs may protect the nasopharyngeal epithelial cells from apoptotic insults, we treated the EBER-expressing NP69 cells with a dsRNA analogue, poly(l).poly(C) (plC), to activate PKR in cells and examined for their responses. Lower level of PKR phosphorylation and elevation of Bcl-2 were observed in EBER-expressing NP69 cells. In addition, other apoptotic markers including the cleaved forms of caspase-3 and poly(ADP)ribose polymerase (PARP) were found to be lower in EBER-expressing NP69 cells after treatment with plC. Lower phosphorylation levels of p38 MARK (mitogen-activated protein kinase) and c-jun were also observed in EBER-expressing NP cells. Our results suggest that EBER expression may confer an apoptotic-resistant phenotype in immortalized nasopharyngeal epithelial cells. © 2005 Wiley-Liss, Inc.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0899-1987/en_HK
dc.relation.ispartofMolecular Carcinogenesisen_HK
dc.rightsMolecular Carcinogenesis. Copyright © John Wiley & Sons, Inc.en_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshApoptosisen_HK
dc.subject.meshCell Line, Transformeden_HK
dc.subject.meshCell Transplantationen_HK
dc.subject.meshEpithelial Cells - virologyen_HK
dc.subject.meshEpstein-Barr Virus Infections - complicationsen_HK
dc.subject.meshHerpesvirus 4, Human - isolation & purificationen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Nudeen_HK
dc.subject.meshNasopharynx - virologyen_HK
dc.subject.meshPhosphorylationen_HK
dc.subject.meshRNA, Viral - analysisen_HK
dc.subject.meshTransfectionen_HK
dc.titleStable expression of EBERs in immortalized nasopharyngeal epithelial cells confers resistance to apoptotic stressen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0899-1987&volume=44&spage=92&epage=101&date=2005&atitle=Stable+expression+of+EBERs+in+immortalized+nasopharyngeal+epithelial+cells+confers+resistance+to+apoptotic+stress.en_HK
dc.identifier.emailChang, RCC:rccchang@hkucc.hku.hken_HK
dc.identifier.emailJin, DY:dyjin@hkucc.hku.hken_HK
dc.identifier.emailWong, YC:ycwong@hkucc.hku.hken_HK
dc.identifier.emailTsao, SW:gswtsao@hkucc.hku.hken_HK
dc.identifier.authorityChang, RCC=rp00470en_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/mc.20133en_HK
dc.identifier.pmid16086371-
dc.identifier.scopuseid_2-s2.0-25844440031en_HK
dc.identifier.hkuros109443en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-25844440031&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume44en_HK
dc.identifier.issue2en_HK
dc.identifier.spage92en_HK
dc.identifier.epage101en_HK
dc.identifier.isiWOS:000232075800003-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridWong, HL=7402862563en_HK
dc.identifier.scopusauthoridWang, X=7501854829en_HK
dc.identifier.scopusauthoridChang, RCC=7403713410en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridFeng, H=7401736336en_HK
dc.identifier.scopusauthoridWang, Q=7406910452en_HK
dc.identifier.scopusauthoridLo, KW=7402101603en_HK
dc.identifier.scopusauthoridHuang, DP=7403891486en_HK
dc.identifier.scopusauthoridYuen, PW=7103124007en_HK
dc.identifier.scopusauthoridTakada, K=7403090730en_HK
dc.identifier.scopusauthoridWong, YC=7403041798en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK

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