Functional role of PPP3CB in neuroblastoma and potential anti-tumor effect of calcineurin inhibitor on neuroblastoma

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10933
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatric surgery
• 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)
• 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)
• 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)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 神経芽腫 / PPP3CB / calcineurin inhibitor

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.

Free Research Field

分子腫瘍学