The investigation of cell-cycle dependent expression of PAX3-FOXO1A in Rhabdomyosarcoma.

2014 Fiscal Year Final Research Report

• 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
• Keywords: PAX3-FOXO1 / 胞巣型横紋筋肉腫

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.

Free Research Field

小児固形腫瘍