Abstract 1300: The potential role of NF-κB activation in the immortalization of nasopharyngeal epithelial cells.

Abstract

Abstract Nasopharyngeal carcinoma (NPC) is a common cancer among Southern Chinese. Many molecular and cellular events, particularly those occurring at the early stage of the NPC development, have not been well defined. Immortalization is a pre-requisite property of cancer cells and is regarded as an early event in human carcinogenesis. Defining and understanding these molecular and cellular events could provide us important insights to the early events involved in the carcinogenesis process. Our lab has established multiple immortalized nasopharyngeal epithelial (NP) cell lines using telomerase alone or in combination with other genetic elements including Bmi-1, cyclin D1 and knocking down p16. We observed that NF-Kappa B are commonly activated in immortalized cells compared to primary cells. Immunofluorescence staining and western blotting assay revealed activation of canonical NF-kappa B pathway in these immortalized nasopharyngeal epithelial cell lines with nuclear translocation of NF-kappa B p65 subunit. Interestingly, EGFR is also commonly expressed in our immortalized nasopharyngeal epithelial cells and may contribute to the constitutive activation of NF-kappa B in immortalized nasopharyngeal epithelial cells. Noteworthy, Epstein - Barr Virus (EBV) infection is closely associated with NPC development. There are studies reporting that activation of NF-kappa B and overexpression of EGFR are derived by EBV encoded LMP1 in NPC (Miller et al. Oncogene. 16, 1998). Our data also show LMP1 could induce NF-kappa B activation and EGFR overexpression in NPC cell line. Thus, the activation of NF-kappa B and overexpression of EGFR may be an important component of EBV infection in epithelial cells and contributing to the development of NPC. We further showed that activation of NF-kappa B signaling appears to be essential for the survival of immortalized nasopharyngeal epithelial cells as inhibition of NF-kappa B activity by a specific inhibitor (Nemo binding domain peptide), could selectively inhibit growth of the immortalized nasopharyngeal epithelial cells but not in primary nasopharyngeal epithelial cells. To study the functional interaction of NF-kappa B activation with EGFR, we have examined if EGFR overexpression may support immortalization of nasopharyngeal epithelial cells. We observed that functional EGFR could facilitate cell growth and protect cells from apoptosis. We are now exploring if activation of NF-kappa B and EGFR overexpression may be functionally related during immortalization of nasopharyngeal epithelial cells appears. Citation Format: Dandan Zhu, Yim Ling Yip, Wen Deng, Chi Man Tsang, Lai Man Cheung, Sai Wah Tsao. The potential role of NF-κB activation in the immortalization of nasopharyngeal epithelial cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1300. doi:10.1158/1538-7445.AM2013-1300 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.