期刊
INTERNATIONAL JOURNAL OF CANCER
卷 138, 期 5, 页码 1175-1185出版社
WILEY-BLACKWELL
DOI: 10.1002/ijc.29850
关键词
NF-kappa B; immortalization; mTOR; ERK1/2; nasopharyngeal carcinoma
类别
资金
- General Research Fund [HKU 779810M]
- Health and Medical Research Fund of Hong Kong [12110782]
- AoE grant [AoE/M-06/08]
- TBRS [T12-401/13-R]
NF-kappa B 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-kappa B is common in NPC and may contribute to NPC development. The role of NF-kappa B activation in immortalization of nasopharyngeal epithelial (NPE) cells, which may represent an early event in NPC pathogenesis, is unknown. Examination of NF-kappa B 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-kappa B signaling is a common phenotype in telomerase-immortalized NPE cell lines. Our results suggest that NF-kappa B activation promotes the growth of telomerase-immortalized NPE cells, and suppression of NF-kappa B activity inhibits their proliferation. Furthermore, we observed upregulation of c-Myc, IL-6 and Bmi-1 in our immortalized NPE cells. Inhibition of NF-kappa B downregulated expression of c-Myc, IL-6 and Bmi-1, suggesting that they are downstream events of NF-kappa B activation in immortalized NPE cells. We further delineated that EGFR/MEK/ERK/IKK/mTORC1 is the key upstream pathway of NF-kappa B 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-kappa B activation and elucidation of its activation mechanism in immortalized NPE cells may reveal novel therapeutic targets for treatment and prevention of NPC.
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