Identification of ALK-related ovarian cancer
| Project/Area Number |
18K15092
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 49020:Human pathology-related
|
|---|
| Research Institution | Kitasato University |
|---|
Principal Investigator |
Inoue Hisako 北里大学, 医学部, 講師 (20813504)
|
|---|
| Project Period (FY) |
2018-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
|---|
| Keywords | ALK / 卵巣がん / 神経内分泌 / 卵巣漿液性癌 / 神経内分泌分化 / 卵巣癌 / HuC / 次世代シークエンサー / 神経内分泌マーカー / ovarian cancer |
|---|
| Outline of Final Research Achievements |
ALK immunoreactivity was significantly higher in high-grade serous carcinoma(HGSC) and was significantly associated with several unfavorable clinicopathological factors. HGSC cell lines stably overexpressing ALK exhibited increased cell proliferation, enhanced cancer stem cell features, and accelerated cell mobility, whereas these phenotypes were abrogated in ALK-knockdown (KD) cells. Expression of ELAVL3(HuC), as well as Sox2 and Sox3, were significantly increased in cells overexpressing ALK. Overexpression of Sox2 or Sox3 also enhanced both ALK and ELAVL3 promoter activities. Finally, ALK overexpression was due to increased expression of neuroendocrine markers including synaptophysin, CD56, and BCL2 in HGCS tissues. These findings suggest that overexpression of full-length ALK may influence the biological behavior of HGSC through cooperation with ELAVL3 and Sox factors, leading to establishment and maintenance of the aggressive phenotypic characteristics of HGSC.
|
| Academic Significance and Societal Importance of the Research Achievements |
①卵巣癌を「ALK遺伝子関連情報伝達異常」という観点からその生物学的特性、特にEMT/癌幹細胞化機構との関連性を分子病理学的に解析し、ALK関連卵巣癌という新たなカテゴリーを提唱する。②卵巣癌のALK発現と臨床病理学的因子との関連性から新たな予後予測システムを構築する。③ALK阻害剤などの分子標的薬や小化学化合物によるALK陽性卵巣癌の新規治療法開発の基盤を築く。
|
Report
(5 results)
Research Products
(3 results)
-
[Journal Article] Anaplastic Lymphoma Kinase Overexpression Is Associated with Aggressive Phenotypic Characteristics of Ovarian High-Grade Serous Carcinoma2021
Author(s)
Matsumoto T, Oda Y, Hasegawa Y, Hashimura M, Oguri Y, Inoue H, Yokoi A, Tochimoto M, Nakagawa M, Jiang Z, Saegusa M.
-
Journal Title
Am J Pathol
Volume: 191
Issue: 10
Pages: 1837-1837
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
