| Budget Amount *help |
¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Outline of Final Research Achievements |
Nasal NK/T-cell lymphoma (NNKTL) is closely associated with Epstein-Barr virus (EBV) and characterized by poor prognosis resulting from rapid progression of the lesion in affected organs. NNKTL is categorized as type II latency of EBV infection and the lymphoma cells express EBV-encoded LMP1, which is regarded as an oncoprotein. Here, we show that NNKTL cells expressed BIRC3, survivin, and XIAP, which are members of inhibitor of apoptosis (IAP) family. Of these, survivin was upregulated by LMP1 in NNKTL cells, and inhibition of survivin in NNKTL cells by several inhibitors lead to decrease in cell proliferation dose-dependently. Moreover, mithramycin, one of these inhibitors, significantly inhibited the growth of established tumor in NOG mice. Our results suggest that LMP1 upregulates survivin expression, and this upregulation is essential for NNKTL growth. Thus, targeting survivin by using mithramycin might be an effective approach to treat NNKTL that is hallmarked by poor prognosis.
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