Project/Area Number |
25893202
|
Research Category |
Grant-in-Aid for Research Activity Start-up
|
Allocation Type | Single-year Grants |
Research Field |
Pediatrics
|
Research Institution | Kyoto Prefectural University of Medicine |
Principal Investigator |
KIKUCHI ken 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40453104)
|
Project Period (FY) |
2013-08-30 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
Keywords | PAX3-FOXO1 / 胞巣型横紋筋肉腫 / PAX3-FOXO1A / チェックポイントアダプテーション |
Outline of Final Research Achievements |
Rhabdomyosarcoma falls into one of two biologically distinct subgroups represented by embryonal or alveolar histology (ARMS), which harbors a PAX3-FOXO1 fusion gene and has an extremely poor prognosis. Murine ARMS primary cultures were obtained from the Myf6Cre, PAX3-FOXO1, p53 conditional mouse model of ARMS. To elucidate the dynamical function of PAX3-FOXO1, time-lapse experiments, cell cycle analysis, QPCR, western blotting, immunohistochemistry, mRNA array and in vivo transplantation experiments were performed using murine ARMS primary cell culture with or without PAX3-FOXO1 knockdown treated by irradiation, or selected for ploidy using hoechst33342 sorted cell cycle-specific cells. The expression level of PAX3-FOXO1 was discovered to be dynamic and to vary during the cell cycle in murine and human ARMS cells. PAX3-FOXO1 is enriched in G2 and triggers at transcriptional program conducive to checkpoint adaptation in genome-wide expression analysis and QPCR.
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