Identification of the genes involved in the tumorigenesis and spontaneous regression in neuroblastoma model mice

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590377
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Nagoya University
• Principal Investigator: KISHIDA Satoshi 名古屋大学, 医学(系)研究科(研究院), 助教 (20402563)
• Co-Investigator(Kenkyū-buntansha): KADOMATSU Kenji 名古屋大学, 大学院医学系研究科, 教授 (80204519)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 神経芽腫 / モデルマウス

Outline of Final Research Achievements

In this research, we tried to identify the genes involved in the tumorigenesis of neuroblastoma, one of the malignant pediatric solid tumors. Based on our comprehensive data acquired from MYCN transgenic (Tg) mice, we identified two genes, NeuroD1 and H1FX. Both were highly expressed in the early lesions of MYCN Tg mice. We showed that NeuroD1 directly induced the transcription of ALK, an important predisposeition gene in neuroblastoma. NeuroD1-ALK axis promotes the proliferation of neuroblastoma cells. On the other hand, H1FX seems to be involved in the early development of sympathetic neurons. H1FX was highly and specifically expressed in totally undifferentiated neuroblast in vivo, and disappeared after differentiation. Interestingly, the expression of H1FX in patients was closely correlated with that of Midkine, a growth factor involved in neuroblastoma tumorigenesis. H1FX could be a target of midkine signaling.

Free Research Field

分子生物学