| Project/Area Number |
13671526
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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 |
Orthopaedic surgery
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
YOSHIDA Koichi Sapporo Medical University, School of Medicine, Biology, Professor, 医学部, 教授 (60117653)
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| Co-Investigator(Kenkyū-buntansha) |
WADA Takuro Sapporo Medical University, School of Medicine, Orthopedic Surgery, Associate Professor, 医学部, 助教授 (00244369)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | sarcoma / mouse model of disease / chromosome translocation / fusion gene / cre-loxP DNA recombination / transgenic mouse / cancer / ETS transcription factor / Cre-1oxP DNA組み換え |
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| Research Abstract |
The purposes of this study is to isolate a model mouse generating Ewing sarcoma and peripheral neuroectodermal tumor (PNET) by expressing the sarcoma-specific EWS-FLI fusion oncogene in the mouse tissue limited for generation of sarcoma, and to identify the genes regulated by tumor-specific transcription factor, the product of EWS-FLI fusion oncogene. Two EWS-FLI transgenic mouse strains with fusion oncogene were isolated and found to be reproductive and able to grow up without any significant failures. To allow DNA recombination in vivo by the Cre-loxP techniques, EWS-FLI mice were crossbred with the Cre transgenic mice manipulated to express the DNA recombinase in neural crest-derived cells. Since mice with the recombined DNA yielded at lower frequency, we were currently unable to determine whether tumor is generated or not. By breeding a different line of EWS-FLI mouse strains, the birth of recombinant mice will be improved. On the other hand, we found several genes whose expressions were altered with the sarcoma-specific fusion oncogene but not with its normal counterpart. One is the extra-cellular matrix component Tenascin-C associated with tumor progression. The other is transcription factor Id2. Their biological significance in Ewing sarcoma was investigated (Genes Chromosomes & Cancer 2003 ; Oncogene 2002). Also we found up-regulation of c-myc and down-regulation of TGF-beta2 and Smad3 expressions by fusion oncogene. These may be associated with higher proliferating potential of Ewing sarcoma cells. To elucidate the mechanism of sarcoma-genesis, further analysis of target genes will be required.
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