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Article: Significance of NF-kB activation in immortalization of nasopharyngeal epithelial cells

TitleSignificance of NF-kB activation in immortalization of nasopharyngeal epithelial cells
Authors
Issue Date2016
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
Citation
International Journal of Cancer, 2016, v. 138 n. 5, p. 1175-1185 How to Cite?
AbstractNF-κB is a key regulator of inflammatory response and is frequently activated in human cancer including the undifferentiated nasopharyngeal carcinoma (NPC), which is common in Southern China including Hong Kong. Activation of NF-κB is common in NPC and may contribute to NPC development. The role of NF-κB activation in immortalization of nasopharyngeal epithelial (NPE) cells, which may represent an early event in NPC pathogenesis, is unknown. Examination of NF-κB activation in immortalization of NPE cells is of particular interest as the site of NPC is often heavily infiltrated with inflammatory cellular components. We found that constitutive activation of NF-κB signaling is a common phenotype in telomerase-immortalized NPE cell lines. Our results suggest that NF-κB activation promotes the growth of telomerase-immortalized NPE cells, and suppression of NF-κB activity inhibits their proliferation. Furthermore, we observed upregulation of c-Myc, IL-6 and Bmi-1 in our immortalized NPE cells. Inhibition of NF-κB downregulated expression of c-Myc, IL-6 and Bmi-1, suggesting that they are downstream events of NF-κB activation in immortalized NPE cells. We further delineated that EGFR/MEK/ERK/IKK/mTORC1 is the key upstream pathway of NF-κB activation in immortalized NPE cells. Elucidation of events underlying immortalization of NPE cells may provide insights into early events in pathogenesis of NPC. The identification of NF-κB activation and elucidation of its activation mechanism in immortalized NPE cells may reveal novel therapeutic targets for treatment and prevention of NPC. What's new? Activation of NF-κB is a common molecular feature in nasopharyngeal cancer (NPC). Yet, it remains unclear whether nuclear factor signaling, through its anti-apoptotic and pro-survival activities, influences the immortalization of nasopharyngeal epithelial (NPE) cells, an essential event in NPC development. In this study, the canonical NF-κB pathway was observed as being constitutively activated in NPE cells immortalized via ectopic telomerase expression. Activation of EGFR was identified as a key upstream event leading to MEK/ERK/IKK/mTOR/NF-κB signaling. Knowledge of this pathway and its role in facilitating NPE cell proliferation could help shed light on early events in NPC. © 2015 UICC.
Persistent Identifierhttp://hdl.handle.net/10722/220048
ISSN
2015 Impact Factor: 5.531
2015 SCImago Journal Rankings: 2.657

 

DC FieldValueLanguage
dc.contributor.authorZHU, D-
dc.contributor.authorZHANG, J-
dc.contributor.authorDeng, W-
dc.contributor.authorYip, YL-
dc.contributor.authorLung, HL-
dc.contributor.authorTsang, CM-
dc.contributor.authorLaw, WT-
dc.contributor.authorYang, J-
dc.contributor.authorLau, MY-
dc.contributor.authorLung, ML-
dc.contributor.authorCheung, A-
dc.contributor.authorTsao, GSW-
dc.date.accessioned2015-10-16T06:27:46Z-
dc.date.available2015-10-16T06:27:46Z-
dc.date.issued2016-
dc.identifier.citationInternational Journal of Cancer, 2016, v. 138 n. 5, p. 1175-1185-
dc.identifier.issn0020-7136-
dc.identifier.urihttp://hdl.handle.net/10722/220048-
dc.description.abstractNF-κB is a key regulator of inflammatory response and is frequently activated in human cancer including the undifferentiated nasopharyngeal carcinoma (NPC), which is common in Southern China including Hong Kong. Activation of NF-κB is common in NPC and may contribute to NPC development. The role of NF-κB activation in immortalization of nasopharyngeal epithelial (NPE) cells, which may represent an early event in NPC pathogenesis, is unknown. Examination of NF-κB activation in immortalization of NPE cells is of particular interest as the site of NPC is often heavily infiltrated with inflammatory cellular components. We found that constitutive activation of NF-κB signaling is a common phenotype in telomerase-immortalized NPE cell lines. Our results suggest that NF-κB activation promotes the growth of telomerase-immortalized NPE cells, and suppression of NF-κB activity inhibits their proliferation. Furthermore, we observed upregulation of c-Myc, IL-6 and Bmi-1 in our immortalized NPE cells. Inhibition of NF-κB downregulated expression of c-Myc, IL-6 and Bmi-1, suggesting that they are downstream events of NF-κB activation in immortalized NPE cells. We further delineated that EGFR/MEK/ERK/IKK/mTORC1 is the key upstream pathway of NF-κB activation in immortalized NPE cells. Elucidation of events underlying immortalization of NPE cells may provide insights into early events in pathogenesis of NPC. The identification of NF-κB activation and elucidation of its activation mechanism in immortalized NPE cells may reveal novel therapeutic targets for treatment and prevention of NPC. What's new? Activation of NF-κB is a common molecular feature in nasopharyngeal cancer (NPC). Yet, it remains unclear whether nuclear factor signaling, through its anti-apoptotic and pro-survival activities, influences the immortalization of nasopharyngeal epithelial (NPE) cells, an essential event in NPC development. In this study, the canonical NF-κB pathway was observed as being constitutively activated in NPE cells immortalized via ectopic telomerase expression. Activation of EGFR was identified as a key upstream event leading to MEK/ERK/IKK/mTOR/NF-κB signaling. Knowledge of this pathway and its role in facilitating NPE cell proliferation could help shed light on early events in NPC. © 2015 UICC.-
dc.languageeng-
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home-
dc.relation.ispartofInternational Journal of Cancer-
dc.rightsInternational Journal of Cancer. Copyright © John Wiley & Sons, Inc.-
dc.rightsSpecial Statement for Preprint only Before publication: 'This is a preprint of an article accepted for publication in [The Journal of Pathology] Copyright © ([year]) ([Pathological Society of Great Britain and Ireland])'. After publication: the preprint notice should be amended to follows: 'This is a preprint of an article published in [include the complete citation information for the final version of the Contribution as published in the print edition of the Journal]' For Cochrane Library/ Cochrane Database of Systematic Reviews, add statement & acknowledgement : ‘This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 20XX, Issue X. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.’ Please include reference to the Review and hyperlink to the original version using the following format e.g. Authors. Title of Review. Cochrane Database of Systematic Reviews 20XX, Issue #. Art. No.: CD00XXXX. DOI: 10.1002/14651858.CD00XXXX (insert persistent link to the article by using the URL: http://dx.doi.org/10.1002/14651858.CD00XXXX) (This statement should refer to the most recent issue of the Cochrane Database of Systematic Reviews in which the Review published.)-
dc.titleSignificance of NF-kB activation in immortalization of nasopharyngeal epithelial cells-
dc.typeArticle-
dc.identifier.emailDeng, W: wdeng@hkucc.hku.hk-
dc.identifier.emailYip, YL: yimling@hku.hk-
dc.identifier.emailLung, HL: hllung2@hku.hk-
dc.identifier.emailTsang, CM: annatsan@hku.hk-
dc.identifier.emailYang, J: jiesarah@HKUCC-COM.hku.hk-
dc.identifier.emailLung, ML: mlilung@hku.hk-
dc.identifier.emailCheung, A: lmcheung@hku.hk-
dc.identifier.emailTsao, GSW: gswtsao@hku.hk-
dc.identifier.authorityDeng, W=rp01640-
dc.identifier.authorityLung, HL=rp00299-
dc.identifier.authorityTsang, CM=rp01964-
dc.identifier.authorityLung, ML=rp00300-
dc.identifier.authorityCheung, A=rp00332-
dc.identifier.authorityTsao, GSW=rp00399-
dc.identifier.doi10.1002/ijc.29850-
dc.identifier.pmid26370441-
dc.identifier.scopuseid_2-s2.0-84955489910-
dc.identifier.hkuros255631-
dc.identifier.volume138-
dc.identifier.issue5-
dc.identifier.spage1175-
dc.identifier.epage1185-
dc.publisher.placeUnited States-

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