| Project/Area Number |
18K09307
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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 56040:Obstetrics and gynecology-related
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
NAKAHARA TOMOMI 国立研究開発法人国立がん研究センター, 研究所, 研究員 (60601177)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 子宮頸がん / パピローマウイルス / 腺がん / 発がんモデル / FOXA2 / ヒトパピローマウイルス / p63 / HPV |
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| Outline of Final Research Achievements |
Cervical adenocarcinoma is the second most common pathological subtype of cervical cancer after squamous cell carcinoma (SCC). To gain insights into molecular background of adenocarcinoma, we aimed to establish an in vitro carcinogenesis model of adenocarcinoma. We previously reported the establishment of an in vitro model for cervical SCC by introducing defined viral and cellular oncogenes, HPV16 E6 and E7, c-MYC and activated RAS to human cervical keratinocytes. In this study, the expression of potential lineage-specifying factors was additionally introduced, and the cell properties associated with the cell lineage were analyzed. In the cells expressing FOXA2, apparent changes in the cell property were observed, including elevated expression of columnar cell markers. Strikingly, the histopathology of tumors and organoids expressing FOXA2 resembled cervical adenocarcinoma, proposing that FOXA2 plays a vital role in dictating the histopathology of cervical cancers.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで未解明であった子宮頸がん腺がんの発がん過程において、転写因子のFOXA2が子宮頸がんの病理学的特徴を決定する重要な因子の一つであることを明らかにした。近年の腺がん増加は、その前駆病変の特徴があまり明らかでなく、早期発見が困難であることが一因とされている。本研究で作成した腺がんの発がん過程を再現する培養モデルは、腺がん前駆病変の詳細解析を可能にし、それに基づく早期診断法の開発や、腺がんの治療抵抗性の分子機構を解明し、新規治療法の開発を推進する基盤となる。
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