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Article: Efficient immortalization of primary nasopharyngeal epithelial cells for EBV infection study.

TitleEfficient immortalization of primary nasopharyngeal epithelial cells for EBV infection study.
Authors
Issue Date2013
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PLoS One, 2013, v. 8 n. 10, article no. e78395 How to Cite?
AbstractNasopharyngeal carcinoma (NPC) is common among southern Chinese including the ethnic Cantonese population living in Hong Kong. Epstein-Barr virus (EBV) infection is detected in all undifferentiated type of NPC in this endemic region. Establishment of stable and latent EBV infection in premalignant nasopharyngeal epithelial cells is an early event in NPC development and may contribute to its pathogenesis. Immortalized primary nasopharyngeal epithelial cells represent an important tool for investigation of EBV infection and its tumorigenic potential in this special type of epithelial cells. However, the limited availability and small sizes of nasopharyngeal biopsies have seriously restricted the establishment of primary nasopharyngeal epithelial cells for immortalization. A reliable and effective method to immortalize primary nasopharyngeal epithelial cells will provide unrestricted materials for EBV infection studies. An earlier study has reported that Bmi-1 expression could immortalize primary nasopharyngeal epithelial cells. However, its efficiency and actions in immortalization have not been fully characterized. Our studies showed that Bmi-1 expression alone has limited ability to immortalize primary nasopharyngeal epithelial cells and additional events are often required for its immortalization action. We have identified some of the key events associated with the immortalization of primary nasopharyngeal epithelial cells. Efficient immortalization of nasopharyngeal epithelial cells could be reproducibly and efficiently achieved by the combined actions of Bmi-1 expression, activation of telomerase and silencing of p16 gene. Activation of MAPK signaling and gene expression downstream of Bmi-1 were detected in the immortalized nasopharyngeal epithelial cells and may play a role in immortalization. Furthermore, these newly immortalized nasopharyngeal epithelial cells are susceptible to EBV infection and supported a type II latent EBV infection program characteristic of EBV-infected nasopharyngeal carcinoma. The establishment of an efficient method to immortalize primary nasopharyngeal epithelial cells will facilitate the investigation into the role of EBV infection in pathogenesis of nasopharyngeal carcinoma.
Persistent Identifierhttp://hdl.handle.net/10722/198977
ISSN
2023 Impact Factor: 2.9
2023 SCImago Journal Rankings: 0.839
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYip, YLen_US
dc.contributor.authorPang, PSen_US
dc.contributor.authorDeng, Wen_US
dc.contributor.authorTsang, CMen_US
dc.contributor.authorZeng, Men_US
dc.contributor.authorHau, PMen_US
dc.contributor.authorMan, Cen_US
dc.contributor.authorJin, Yen_US
dc.contributor.authorYuen, APWen_US
dc.contributor.authorTsao, GSWen_US
dc.date.accessioned2014-07-22T00:58:48Z-
dc.date.available2014-07-22T00:58:48Z-
dc.date.issued2013en_US
dc.identifier.citationPLoS One, 2013, v. 8 n. 10, article no. e78395en_US
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/198977-
dc.description.abstractNasopharyngeal carcinoma (NPC) is common among southern Chinese including the ethnic Cantonese population living in Hong Kong. Epstein-Barr virus (EBV) infection is detected in all undifferentiated type of NPC in this endemic region. Establishment of stable and latent EBV infection in premalignant nasopharyngeal epithelial cells is an early event in NPC development and may contribute to its pathogenesis. Immortalized primary nasopharyngeal epithelial cells represent an important tool for investigation of EBV infection and its tumorigenic potential in this special type of epithelial cells. However, the limited availability and small sizes of nasopharyngeal biopsies have seriously restricted the establishment of primary nasopharyngeal epithelial cells for immortalization. A reliable and effective method to immortalize primary nasopharyngeal epithelial cells will provide unrestricted materials for EBV infection studies. An earlier study has reported that Bmi-1 expression could immortalize primary nasopharyngeal epithelial cells. However, its efficiency and actions in immortalization have not been fully characterized. Our studies showed that Bmi-1 expression alone has limited ability to immortalize primary nasopharyngeal epithelial cells and additional events are often required for its immortalization action. We have identified some of the key events associated with the immortalization of primary nasopharyngeal epithelial cells. Efficient immortalization of nasopharyngeal epithelial cells could be reproducibly and efficiently achieved by the combined actions of Bmi-1 expression, activation of telomerase and silencing of p16 gene. Activation of MAPK signaling and gene expression downstream of Bmi-1 were detected in the immortalized nasopharyngeal epithelial cells and may play a role in immortalization. Furthermore, these newly immortalized nasopharyngeal epithelial cells are susceptible to EBV infection and supported a type II latent EBV infection program characteristic of EBV-infected nasopharyngeal carcinoma. The establishment of an efficient method to immortalize primary nasopharyngeal epithelial cells will facilitate the investigation into the role of EBV infection in pathogenesis of nasopharyngeal carcinoma.-
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action-
dc.relation.ispartofPLoS ONEen_US
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subject.meshEpithelial Cells - metabolism - pathology - virology-
dc.subject.meshHerpesvirus 4, Human - physiology-
dc.subject.meshNasal Cavity - metabolism - pathology - virology-
dc.subject.meshNasal Mucosa - metabolism - pathology - virology-
dc.subject.meshPharynx - metabolism - pathology - virology-
dc.titleEfficient immortalization of primary nasopharyngeal epithelial cells for EBV infection study.en_US
dc.typeArticleen_US
dc.identifier.emailYip, YL: elaineyip@graduate.hku.hken_US
dc.identifier.emailPang, PS: emilypsp@hku.hken_US
dc.identifier.emailDeng, W: wdeng@hkucc.hku.hken_US
dc.identifier.emailTsang, CM: anna0226@graduate.hku.hken_US
dc.identifier.emailHau, PM: tomhau10@hku.hken_US
dc.identifier.emailTsao, GSW: gswtsao@hku.hken_US
dc.identifier.authorityDeng, W=rp01640en_US
dc.identifier.authorityTsao, GSW=rp01640en_US
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0078395-
dc.identifier.pmid24167620-
dc.identifier.pmcidPMC3805559-
dc.identifier.scopuseid_2-s2.0-84886016074-
dc.identifier.hkuros230728en_US
dc.identifier.volume8en_US
dc.identifier.issue10-
dc.identifier.isiWOS:000326034500081-
dc.publisher.placeUnited States-
dc.identifier.issnl1932-6203-

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