| Project/Area Number |
18K08800
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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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| Review Section |
Basic Section 55040:Respiratory surgery-related
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
本多 彰 東京医科大学, 医学部, 教授 (10468639)
中嶋 英治 東京医科大学, 医学部, 講師 (60366143)
宮崎 照雄 東京医科大学, 医学部, 准教授 (60532687)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 27-ヒドロキシコレステロール / エストロゲン受容体 / 肺がん / 肺がん細胞 / アミノ酸代謝 |
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| Outline of Final Research Achievements |
27-hydroxycholesterol (27HC) is synthesized from cholesterol mostly in alveolar macrophage, and promotes the proliferation of breast cancer cells as selective estrogen receptor modulator (SERM). We hypothesized that 27HC modulates ER-positive lung cancer growth. Cell growth of an ERβ-positive lung cell line (H23) was significantly promoted by adding more than 100 nM of 27HC. Besides, the addition of PHTPP, an antagonist of ERβ, canceled the growth promotion due to 27HC. In the tumor region collected from 13 lung cancer patients, 27HC content and the mRNA expressions of ERβ and its target gene c-Myc were significantly higher than in the non-tumor counterpart collected from same patient. These results suggest that 27HC can stimulate the growth of ER-positive lung cancer in vivo. Therefore, the inhibitions of 27HC production and ER activity may be new strategies to suppress the postoperative recurrence of ER-positive lung cancer in both genders.
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| Academic Significance and Societal Importance of the Research Achievements |
肺がんは発生率と死亡率共に，世界的に高く，2018年には210万人が罹患し、180万人が死亡している。本研究における成果は，エストロゲン受容体βの発現が確認された肺がんに対して，27-ヒドロキシコレステロールを合成する肺胞マクロファージの活性化をコントロールする事やエストロゲン受容体βの選択的阻害剤を用いる事で，術後の再発を抑制できる可能性が示唆された。新たな治療方法の開発や、27-ヒドロキシコレステロールが多く存在する他臓器がんでの検討など、応用範囲が広い研究成果と考えられる。
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