| Project/Area Number |
25893008
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
UEDA Seigo 旭川医科大学, 医学部, 助教 (90447102)
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| Project Period (FY) |
2013-08-30 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 鼻性NK/T細胞リンパ腫 / Epstein-Barr virus / BIRC5 / CDK1 / LMP1 / 化学療法 / EBウイルス |
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| Outline of Final Research Achievements |
Nasal NK/T-cell lymphoma (NNKTL) is EBV-related malignancy and has a poor prognosis. An improved understanding of the mechanisms of NNKTL is crucial for identifying new targets of effective treatment modalities for this deadly disease. We found that inhibitors of Sp1 transcription factor dose-dependently decreased cell proliferation of NNKTL cells. This was associated with decrease in BIRC5 and CDK1 expressions and induction of apoptosis and cell-cycle arrest at G2/M phase in NNKTL cells. Knockdown of EBV-encoded LMP1 induced downregulation of CDK1 and BIRC5 expressions and apoptosis in NNKTL cells. Immunohistochemistry detected BIRC5 expression in LMP1-positive lymphoma cells of NNKTL biopsy specimens. Our results suggest that LMP1 upregulates CDK1 and BIRC5 expression, and these upregulations are essential for NNKTL growth. Thus, targeting CDK1 and BIRC5 by using Sp1 inhibitors might be an effective approach to treat NNKTL that is hallmarked by poor prognosis.
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