EWS/ATF1 activates Fos and induces soft tissue sarcomas from neural crest-derived cells
| Project/Area Number |
24592229
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Gifu University |
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Principal Investigator |
OHNO Takatoshi 岐阜大学, 医学(系)研究科(研究院), 准教授 (60281052)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 明細胞肉腫 / 融合遺伝子 / EWS-ATF1 / Fos / 分子標的治療 / トランスジェニックマウス / 軟部肉腫 / EWS/ATF1 |
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| Outline of Final Research Achievements |
Clear cell sarcoma (CCS) is characterized by t(12; 22) translocation, leading to the expression of a chimeric EWS/ATF1 fusion gene. However, little is known about the mechanisms underlying how EWS/ATF1 is involved in the development of CCSs. We generated EWS/ATF1-inducible mice, and examined the effects of EWS/ATF1 expression in adult cells. We show that the forced expression of EWS/ATF1 results in the development of EWS/ATF1-dependent sarcomas in mice. The histology of EWS/ATF1-induced sarcomas resembles that of CCSs and EWS/ATF1-induced tumor cells express CCS-markers, such as Mitf. A lineage tracing experiment revealed that such sarcomas are derived from neural crest-lineage cells. Finally, we found that EWS/ATF1 directly induces Fos in an ERK-independent manner, and demonstrated that the increased Fos expression is important for the active cell proliferations. Our results indicate that FOS could be a promising therapeutic target for the treatment of EWS/ATF1-related sarcomas.
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] EWS/ATF1 activates Fos and induces soft tissue sarcomas from neural crest-derived cells2013
Author(s)
Yamada K, Ohno T, Aoki H, Semi K, Watanabe A, Moritake H, Shiozawa S, Kunisada T, Kobayashi Y, Toguchida J, Shimizu K, Hara A, Yamada Y
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Journal Title
J Clinical Investigation
Volume: 123
Pages: 600-610
Related Report
Peer Reviewed
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[Journal Article] Growth Suppression and Mitotic Defect Induced by JNJ-7706621, an Inhibitor of Cyclin-Dependent Kinases and Aurora Kinases.2012
Author(s)
Matsuhashi A, Ohno T, Kimura M, Hara A, Saio M, Nagano A, Kawai G, Saitou M, Takigami I, Yamada K, Okano Y, Shimizu K.
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Journal Title
Curr Cancer Drug Targets
Volume: 12
Issue: 6
Pages: 625-639
DOI
Related Report
Peer Reviewed
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[Presentation] 小児の骨軟部腫瘍2014
Author(s)
大野貴敏
Organizer
第12回東海小児整形外科研修会
Place of Presentation
名古屋
Year and Date
2014-12-21
Related Report
Invited
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