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Article: Cyclin D1 overexpression supports stable EBV infection in nasopharyngeal epithelial cells

TitleCyclin D1 overexpression supports stable EBV infection in nasopharyngeal epithelial cells
Authors
Issue Date2012
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2012, v. 109 n. 50, p. E3473-E3482 How to Cite?
AbstractUndifferentiated nasopharyngeal carcinomas (NPCs) are commonly present with latent EBV infection. However, events regulating EBV infection at early stages of the disease and the role of EBV in disease pathogenesis are largely undefined. Genetic alterations leading to activation of cyclin D1 signaling in premalignant nasopharyngeal epithelial (NPE) cells have been postulated to predispose cells to EBV infection. We previously reported that loss of p16, a negative regulator of cyclin D1 signaling, is a frequent feature of NPC tumors. Here, we report that early premalignant lesions of nasopharyngeal epithelium overexpress cyclin D1. Furthermore, overexpression of cyclin D1 is closely associated with EBV infection. Therefore we investigated the potential role of cyclin D1 overexpression in dysplastic NPE cells in vitro. In human telomerase reverse transcriptase-immortalized NPE cells, overexpression of cyclin D1 or a p16-resistant form of CDK4 (CDK4(R24C)) suppressed differentiation. This suppression may have implications for the close association of EBV infection with undifferentiated NPC. In these in vitro models, we found that cellular growth arrest and senescence occurred in EBV-infected cell populations immediately after infection. Nevertheless, overexpression of cyclin D1 or a p16-resistant form of CDK4 or knockdown of p16 in the human telomerase reverse transcriptase-immortalized NPE cell lines could counteract the EBV-induced growth arrest and senescence. We conclude that dysregulated expression of cyclin D1 in NPE cells may contribute to NPC pathogenesis by enabling persistent infection of EBV.
Persistent Identifierhttp://hdl.handle.net/10722/185613
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorTsang, CMen_US
dc.contributor.authorYip, YLen_US
dc.contributor.authorLo, KWen_US
dc.contributor.authorDeng, Wen_US
dc.contributor.authorTo, KFen_US
dc.contributor.authorHau, PMen_US
dc.contributor.authorLau, VMYen_US
dc.contributor.authorTakada, Ken_US
dc.contributor.authorLui, VWYen_US
dc.contributor.authorLung, ML-
dc.contributor.authorChen, H-
dc.contributor.authorZeng, M-
dc.contributor.authorMiddeldorp, JM-
dc.contributor.authorCheung, ALM-
dc.contributor.authorTsao, SW-
dc.date.accessioned2013-08-20T11:34:22Z-
dc.date.available2013-08-20T11:34:22Z-
dc.date.issued2012en_US
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2012, v. 109 n. 50, p. E3473-E3482en_US
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/185613-
dc.description.abstractUndifferentiated nasopharyngeal carcinomas (NPCs) are commonly present with latent EBV infection. However, events regulating EBV infection at early stages of the disease and the role of EBV in disease pathogenesis are largely undefined. Genetic alterations leading to activation of cyclin D1 signaling in premalignant nasopharyngeal epithelial (NPE) cells have been postulated to predispose cells to EBV infection. We previously reported that loss of p16, a negative regulator of cyclin D1 signaling, is a frequent feature of NPC tumors. Here, we report that early premalignant lesions of nasopharyngeal epithelium overexpress cyclin D1. Furthermore, overexpression of cyclin D1 is closely associated with EBV infection. Therefore we investigated the potential role of cyclin D1 overexpression in dysplastic NPE cells in vitro. In human telomerase reverse transcriptase-immortalized NPE cells, overexpression of cyclin D1 or a p16-resistant form of CDK4 (CDK4(R24C)) suppressed differentiation. This suppression may have implications for the close association of EBV infection with undifferentiated NPC. In these in vitro models, we found that cellular growth arrest and senescence occurred in EBV-infected cell populations immediately after infection. Nevertheless, overexpression of cyclin D1 or a p16-resistant form of CDK4 or knockdown of p16 in the human telomerase reverse transcriptase-immortalized NPE cell lines could counteract the EBV-induced growth arrest and senescence. We conclude that dysregulated expression of cyclin D1 in NPE cells may contribute to NPC pathogenesis by enabling persistent infection of EBV.-
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshCell Transformation, Neoplastic-
dc.subject.meshCyclin D1 - genetics - metabolism-
dc.subject.meshEpstein-Barr Virus Infections - complications - genetics - metabolism - virology-
dc.subject.meshHerpesvirus 4, Human - genetics - pathogenicity-
dc.subject.meshNasopharynx - metabolism - pathology - virology-
dc.titleCyclin D1 overexpression supports stable EBV infection in nasopharyngeal epithelial cellsen_US
dc.typeArticleen_US
dc.identifier.emailTsang, CM: anna0226@graduate.hku.hken_US
dc.identifier.emailYip, YL: elaineyip@graduate.hku.hken_US
dc.identifier.emailDeng, W: wdeng@hkucc.hku.hken_US
dc.identifier.emailHau, PM: tomhau10@hku.hken_US
dc.identifier.emailLung, ML: mlilung@hku.hk-
dc.identifier.emailChen, H: hlchen@hku.hk-
dc.identifier.emailCheung, ALM: lmcheung@hkucc.hku.hk-
dc.identifier.emailTsao, SW: gswtsao@hkucc.hku.hk-
dc.identifier.authorityDeng, W=rp01640en_US
dc.identifier.authorityLung, ML=rp00300en_US
dc.identifier.authorityChen, H=rp00383-
dc.identifier.authorityCheung, ALM=rp00332-
dc.identifier.authorityTsao, SW=rp00399-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1073/pnas.1202637109-
dc.identifier.pmid23161911-
dc.identifier.pmcidPMC3528537-
dc.identifier.scopuseid_2-s2.0-84870931320-
dc.identifier.hkuros224882en_US
dc.identifier.hkuros217691-
dc.identifier.hkuros217694-
dc.identifier.hkuros217720-
dc.identifier.volume109en_US
dc.identifier.issue50en_US
dc.identifier.spageE3473en_US
dc.identifier.epageE3482en_US
dc.identifier.isiWOS:000312605600015-
dc.publisher.placeUnited States-

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