| Project/Area Number |
20K18160
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 子宮体部類内膜癌 / Foxp4 / Androgen receptor / Androgens / アンドロゲン / Androgen / 増悪化 / Dihydrotestosterone |
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| Outline of Research at the Start |
Foxp4分子発現の体癌の悪性化に対する役割を細胞株、遺伝子改変マウスを用いて検討して子宮体部類内膜癌の悪性化に関する有意義な情報を得、さらに主にAndrogen に着目しFoxp4を制御する因子についても検討して治療薬として先駆的な知見を得る。
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| Outline of Final Research Achievements |
When the expression of Foxp4 and Androgen receptor (AR) was examined for endometrial cancer, it was found that the prognosis was poor in the Foxp4 strongly positive group and the AR weakly positive group. Experiments with human endometrial cancer cell lines also suggested that Foxp4 may promote cell proliferation and scaffold-independent proliferation. Furthermore, it was found that when an AR-expressing human endometrial cancer cell line was prepared and DHT was administered, the expression level of Foxp4 decreased and cell proliferation was suppressed. These results strongly suggest that Foxp4 may be involved in the exacerbation of endometrial cancer, and that androgen may be involved in its regulation, which was supported by experiments using mice.
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| Academic Significance and Societal Importance of the Research Achievements |
子宮内膜癌は罹患率・死亡率ともに増加傾向を示している婦人科悪性腫瘍である。しかし病理組織や画像診断で再発低リスク群と判定されるもリンパ節転移や術後再発をきたす症例の存在が問題となっている。今回の研究でFoxp4の発現が子宮内膜癌の悪性化に関与しており、AndrogenがFoxp4を制御する因子の一つである可能性が強く示唆された。腫瘍の癌化・進展を説明する新たな機序が解明され、今後さらにこれらのシグナル経路に関わる新たな治療法が提案できる可能性がある。
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