Abstract 1046: The role of NF-kB activation in the immortalization of nasopharyngeal epithelial cells

Abstract

Abstract NF-κB is a key regulator of inflammatory response and is frequently activated in human cancers including nasopharyngeal carcinoma (NPC), which is closely associated with Epstein-Barr virus (EBV) infection and a common cancer in Southern China including Hong Kong. However, it is well-established that EBV infection alone is not sufficient for NPC development. Other genetic alterations in host cells and the interaction between EBV infection and host cell microenvironment are required for NPC development. Our group has been involved in illustrating molecular events underlying the immortalization of nasopharyngeal epithelial (NPE) cells. Molecular changes which facilitate immortalization may represent early genetic events in human carcinogenesis. We found that the activation of NF-κB was a common feature in telomerase-immortalized NPE cell lines. We further showed that canonical NF-κB activation pathway was involved in the immortalization of NPE cells. The activation of NF-κB was essential for the proliferation of the immortalized NPE cells because suppression of NF-κB activity could selectively inhibit the proliferation of immortalized but not primary NPE cells. The upregulation of c-Myc and Bmi-1, known to promote cell proliferation, were associated with NF-κB activation in the immortalized NPE cell lines. Interestingly, mTOR was found to be the upstream activator of NF-κB. We further showed that EGFR/Erk(1/2) pathway was the upstream regulator of mTOR/NF-κB pathway, revealing the pathway of EGFR/Erk(1/2)/mTOR/NF-κB for NF-κB activation in telomerase-immortalized NPE cells. Elucidation of specific pathway leading to NF-κB activation in immortalized NPE cells may open up opportunity for early intervention to suppress or prevent NPC development. Citation Format: George Sai-Wah Tsao, Dan Dan Zhu, Jun Zhang, Wen Deng. The role of NF-kB activation in the immortalization of nasopharyngeal epithelial cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1046. doi:10.1158/1538-7445.AM2015-1046