| Project/Area Number |
15591593
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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 School of Medicine, Biology, Professor, 医学部, 教授 (60117653)
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| Co-Investigator(Kenkyū-buntansha) |
WADA Takuro School of Medicine, Orthopedic Surgery, Associate Professor, 医学部, 助教授 (00244369)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Ewing sarcoma / mouse model of disease / fusion oncogene / EWS-FLI / cre-loxP / chromosome translocation / telomerase / ETS transcription factor / 標的遺伝子 / トランスジェニックマウス / Cre-loxP DNA組み換え / PNET / 肉腫 / EWS / ETS |
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| Research Abstract |
A goal of this study is to express the oncogene in mother tissue for Ewing sarcoma-genesis and to isolate a model laboratory mouse. Furthermore, it is to identify a target gene which the EWS-FLI fusion transcription factor controls. We isolated a transgenic mouse of two strains carrying EWS-FLI oncogene. These mice had reproductive potential and were able to propagate in a normal condition. We crossbred these mice with the laboratory mouse which expresses Cre enzyme in neural crest. This allows us to induce a recombination of DNA in vivo and an activation of EWS-FLI oncogene in neural crest-derived cells. Since mouse was not obtained in enough numbers, we were unable to judge sarcoma-genesis. We are going to isolate a different strain of transgenic mouse and crossbreed it with the Cre transgenic mouse again. In the cell line which we introduced the oncogene EWS-FLI into, we found the gene which expression was significantly altered. We made clear by cDNA array method that the tenascin gene, an extra-cellular matrix component, was activated by EWS-FLI. Also we found that a fusion transcription factor activated telomerase gene which is associated with cellular immortalization. We continue manufacture of model laboratory mouse of Ewing sarcoma and are going to examine a role of target gene in development of the neoplasm.
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