Neuroblastoma mouse model developing metastatic tumors

2014 Fiscal Year Final Research Report

• Project/Area Number: 24700957
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Carcinogenesis
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: SUENAGA Yusuke 千葉県がんセンター(研究所), がんゲノムセンター, 研究員 (80581793)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: NCYM / MYCN / neuroblastoma / OCT4 / Myc-nick / stem cell / transgenic mouse / metastasis

Outline of Final Research Achievements

MYCN oncogene has a central role in the genesis and progression of neuroblastomas, and its amplification is associated with an unfavorable prognosis. We have found that NCYM, a MYCN cis-antisense RNA, is evolutionally conserved only in the taxonomic group containing humans and chimpanzees and that the NCYM gene encodes a functional protein in humans. MYCN transgenic mice, which express human MYCN in sympathoadrenal tissues, spontaneously develop neuroblastomas. However, unlike human neuroblastoma, distant metastasis is infrequent. We established MYCN / NCYM double transgenic mice as a new animal model for studying neuroblastoma pathogenesis. We found that NCYM expression promoted both the metastasis and chemo-resistance of the neuroblastomas formed in the double transgenic mice. These results demonstrate that the MYCN / NCYM transgenic mouse may be a suitable model for the screening of the new drugs against high-risk neuroblastomas.

Free Research Field

分子生物学、腫瘍学