| Project/Area Number |
17K08768
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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 |
Experimental pathology
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
OIKAWA Kosuke 和歌山県立医科大学, 医学部, 講師 (70348803)
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| Co-Investigator(Kenkyū-buntansha) |
村垣 泰光 和歌山県立医科大学, 医学部, 教授 (40190904)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 粘液型脂肪肉腫 / がんタンパク / TLS-CHOP / 腫瘍関連メカニズム / 病理学 / 癌 / キメラ遺伝子 |
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| Outline of Final Research Achievements |
The TLS-CHOP fusion oncoprotein resulting from a specific chromosomal translocation is found in majority of human mixoid liposarcomas, and is thought to function as a tumor-specific transcription factor. Previously, we have revealed that TLS-CHOP represses expression of MDA-7 mRNA via induction of DOL54 expression. In this study, we showed that MDA-7 protein is degraded by the ubiquitin-proteasome system in myxoid liposarcoma cells, probably via indcution of PAI-1 expression. Thus, MDA-7 may be strongly repressed at both mRNA and protein levels in myxoid liposarcoma cells. On the other hand, we have also found that MKL-1 knockdown promotes adipocytic differentiation in myxoid liposarcoma cells, suggesting that MKL-1 may be a promising molecular target in differentiation therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
粘液型脂肪肉腫は、中高年の軟部肉腫の中では発生頻度が高いものの1つである。粘液型脂肪肉腫の予後は比較的良いとされているが、手術療法による治療では、発生部位や範囲により機能欠損の問題が生じる。その点、本研究のように、粘液型脂肪肉腫で働く腫瘍関連分子機構の解明とそれに関連した分子治療の新規標的分子の検索は、非侵襲的な治療法の開発につながる。さらに、腫瘍細胞におけるMDA-7の抑制機構の解明に関しては、その機構が他の種類の腫瘍にも共通する可能性が考えられるため、さらなる発展が期待される。
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