Upregulation of members of IAP family in nasal NK/T cell lymphoma

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K20174
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Asahikawa Medical College
• Principal Investigator: Seigo Ueda 旭川医科大学, 医学部, 助教 (90447102)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 鼻性NK/T細胞リンパ腫 / IAPファミリー / EBウイルス / サバイビン / ミトラマイシン

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.

Free Research Field

耳鼻咽喉科