| Project/Area Number |
15K10933
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatric surgery
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| Research Institution | 地方独立行政法人佐賀県医療センター好生館(ライフサイエンス研究所) |
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Principal Investigator |
LI YUANYUAN 地方独立行政法人佐賀県医療センター好生館(ライフサイエンス研究所), ライフサイエンス研究所, 研究員 (00392259)
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| Co-Investigator(Kenkyū-buntansha) |
中川原 章 地方独立行政法人佐賀県医療センター好生館(ライフサイエンス研究所), ライフサイエンス研究所, 理事長 (50117181)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 神経芽腫 / PPP3CB / calcineurin inhibitor / ＰＰＰ３ＣＢ |
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| Outline of Final Research Achievements |
PPP3CB is the catalytic subunit of calcineurin, a calcium-dependent serine/threonine phosphatase. In this study we found that overexpression of wildtype PPP3CB or constitutively active PPP3CB mutant (PPP3CBmut) identified from a neuroblastoma (NB) tumor promoted cell growth in NB cells. PPP3CB and PPP3CBmut activated nuclear factor of activated T-cells (NFAT)2 /NFAT4 transcription factors, Akt and MAPK signaling, resulting in the increase in the expressions of c-Myc, MYCN and β-catenin. Treatment with calcineurin inhibitors (CaIs) suppressed cell proliferation and induced apoptotic cell death in several NB cell lines. Expression of PPP3CB along with those of c-Myc, MYCN and β-catenin was decreased in response to CaIs. Our findings demonstrate that PPP3CB contributes to the aggressive behavior of NB tumors and CaIs have a strong anti-tumor activity in vitro by targeting PPP3CB, suggesting that inhibition of calcineurin activity might have therapeutic potential for high-risk NBs.
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