2007 Fiscal Year Final Research Report Summary
Genetic alterations in nephroblastomas and anti-proliferating effects induced by silencing of the tumor-related genes.
| Project/Area Number |
18591954
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatric surgery
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| Research Institution | Nihon University |
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Principal Investigator |
KUSAFUKA Takeshi Nihon University, School of Medicine, Professor (70263267)
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| Co-Investigator(Kenkyū-buntansha) |
福澤 正洋 大阪大学, 大学院・医学系研究科, 教授 (60165272)
YONEDA Akihiro Osaka University, Graduate School of Medicine, Assistant Professor (30372618)
YONEDA Akihiro Osaka University, Graduate School of Medicine, Professor (30372618)
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| Project Period (FY) |
2006 – 2007
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| Keywords | gene / nephroblastoma / beta-catenin / neuroblastoma / MYCN |
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| Research Abstract |
To investigate how much extent beta-catenin aberration would have positive effect on tumorigenesis of nephroblastomas, normal cDNA of beta-catenin, or various types of mutated sequences were introduced into HEK293 cells derived from the embryonal kidney, and stable clones were established. Three different clones, corresponding to the normal beta-catenin sequence (WT), a point mutation at codon 45 (P45), and an interstitial deletion of the whole exon 3 of the bete-catenin gene (Δ ex3), were selected. Exogenous expressions of the introduced beta-catenins were regulated by administration of doxycycline (DOX) in these cell lines. Subsequent analyses of transcriptional activity using TOPFLASH plasmid system showed that exogenously overexpressed beta-catenins enhanced transcription of the reporter gene regulated through T-cell factor binding site in the WT and P45 cell lines, but not in the Δ ex3. Further investigation, however, failed to show increased cell proliferation in any of these three cell lines, providing no definitive supports to indicate involvement of beta-catenin aberration in the development of nephroblastic tumors.
On the other hand, MYCN gene silencing experiment on a neuroblastoma cell line, NB-1, demonstrated suppressed cell proliferation property accompanied by apoptosis and differentiation of the cells. Because the MYCN gene is amplified and overexpressed in NB-1 similar to many other clinical tumors, strategy to silence this gene may lead to a new hopeful therapy
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[Journal Article] Silencing of MYCN by RNA interference induces growth inhibition, apoptotic activity and cell differentiation in a neuroblastoma cell line with MYCN amplification2007
Author(s)
Nara, K., Kusafuka, T., Yoneda, A., Oue, T., Sangkhathat, S., Fukuzawa, M
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Journal Title
Int J Oncol 30(5)
Pages: 1189-96
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Silencing MYCN by RNA Interference Induces Growth Inhibition, Apoptotic Activity and Cell Differentiation in a Neuroblastoma Cell Line with MYCN Amplification2006
Author(s)
Nara, K., Kusafuka, T., Yoneda, A., Sangkhathat, S., Fukuzawa, M
Organizer
Advances in Neuroblastoma Research2006(ANR)
Place of Presentation
Los Angeles
Year and Date
20060518-20
Description
「研究成果報告書概要(欧文)」より
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