Abstract 230: LMP1 function in NK/T-cell lymphoma

Abstract BACKGROUND: Because NK/T-cell lymphoma was closely associated with EBV LMP1 (latent membrane protein-1) which can directly activate NF-κB-mediated oncoproteins, therefore, in this study determined whether bortezomib (proteasome inhibitor) alone or combined with irradiation affect cytotoxicity and related mechanism in NK/T-cell lymphoma and malignant lymphoid cell lines. Beside, recently LMP1 has been introduced ambivalent function, because it's also up-regulation of Fas signaling. However, lack of information when these are activated by various stimulations. Therefore, in this study, we showed that bortezomib can enhance up-regulation of LMP1 as pro-apoptotic protein in EBV LMP1 expressed cell lines. MATERIAL & METHOD: Human NK/T-cell lymphoma cells (Hank-1), NK-cell lymphoma (NK-92), T-cell lymphoma cells (Jurkat), and Burkitt lymphoma cells (Raji and Jijoye) were used. Bortezomib and irradiation were treated alone or combined, and tumor cell growth and apoptosis were measured by MTT assay and FACS respectively. Apoptosis and its associated protein expression levels were measured by Western blot assay. Interaction of LMP1 and Fas were evaluated by immuno-precipitation and protein ligation assay. RESULTS: Cell death by combining of bortezomib and irradiation synergistically inducing in LMP1 expressed Hank-1 than no LMP1 expressed NK-92 cells. To understand the mechanism of bortezomib regulated LMP1 and Fas, we examined that activated LMP1 by bortezomib enhanced effect of irradiation inducing cytotoxicity. Combined treatment of bortezomib and irradiation up-regulated LMP1 and Fas which composed binding complex, activating Fas-related molecules. In this regard, LMP1 may have paradoxal behavior. These results provided that combination of bortezomib and irradiation enhanced LMP1 as pro-apoptotic function, leading to degradation of NF-κB and resulted caspase activation in EBV LMP1 expressed cancer cell lines. CONCLUSION: LMP1 is able to inducing NF-κB in normal condition as oncoprotein, however bortezomib could up-regulate LMP1, its binding with Fas in EBV LMP1 expressed lymphoid cancer cell lines. Therefore, combination of bortezomib and irradiation is suggested as potential therapy not only in NK/T-cell lymphoma but also LMP1 expressed lymphoma and tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 230.