title: Significance of NF-κB activation in immortalization of nasopharyngeal epithelial cells.
abstract: NF-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.
authors.affiliation: School of Biomedical Sciences and Center for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Dan Dan
authors.initials: DD
authors.lastname: Zhu
authors.affiliation: School of Biomedical Sciences and Center for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Biomedical Sciences and Center for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.|School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Deng
authors.affiliation: School of Biomedical Sciences and Center for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Yim Ling
authors.initials: YL
authors.lastname: Yip
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Hong Lok
authors.initials: HL
authors.lastname: Lung
authors.affiliation: School of Biomedical Sciences and Center for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Chi Man
authors.initials: CM
authors.lastname: Tsang
authors.affiliation: School of Biomedical Sciences and Center for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Wai Tak
authors.initials: WT
authors.lastname: Law
authors.affiliation: School of Biomedical Sciences and Center for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: School of Biomedical Sciences and Center for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Victoria Ming Yi
authors.initials: VM
authors.lastname: Lau
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Wai Ho
authors.initials: WH
authors.lastname: Shuen
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Maria Li
authors.initials: ML
authors.lastname: Lung
authors.affiliation: School of Biomedical Sciences and Center for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Annie Lai Man
authors.initials: AL
authors.lastname: Cheung
authors.affiliation: School of Biomedical Sciences and Center for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Sai Wah
authors.initials: SW
authors.lastname: Tsao
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004847:Epithelial Cells; D066246:ErbB Receptors / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology*; D009303:Nasopharyngeal Neoplasms / Q000209:etiology*; D009305:Nasopharynx / Q000473:pathology*; D063150:Polycomb Repressive Complex 1 / Q000502:physiology; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000502:physiology
chemical_list: C069077:BMI1 protein, human; D046912:Multiprotein Complexes; D016328:NF-kappa B; D063150:Polycomb Repressive Complex 1; D066246:ErbB Receptors; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: ERK1/2; NF-κB; immortalization; mTOR; nasopharyngeal carcinoma