Pathogenesis of endometriosis and its malignant transformation.
Project/Area Number |
26293361
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Obstetrics and gynecology
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Research Institution | Nara Medical University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
吉元 千陽 奈良県立医科大学, 医学部, 助教 (00526725)
重富 洋志 奈良県立医科大学, 医学部, 助教 (20433336)
吉田 昭三 奈良県立医科大学, 医学部, 研究員 (40347555)
小池 奈月 奈良県立医科大学, 医学部, 助教 (20526785)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2015: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2014: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
|
Keywords | 子宮内膜症 / 卵巣癌 / 癌 / 子宮内膜症癌化 |
Outline of Final Research Achievements |
Hepatocyte nuclear factor (HNF)-1beta enhances checkpoint kinase 1 (Chk1) activation and promotes G2/M cell cycle progression in ovarian clear cell carcinoma (CCC) following exposure to diverse genotoxic agents including bleomycin. Loss-of-function studies using RNAi-mediated gene silencing indicated that HNF-1beta facilitated the Claspin expression after treatment with a genotoxic agent bleomycin, resulting in accumulation of phosphorylated Chk1 (p-Chk1) and promotion of survival in CCC cell lines. This study showed for the first time that USP28, a de-ubiquitinase crucial for Claspin expression, is one target gene of HNF-1beta. Knockdown of endogenous USP28 suppressed the Claspin and p-Chk1 expression and cell viability. Our findings identify a novel pathway of the HNF-1beta―Claspin―Chk1 axis in checkpoint signal amplification in response to DNA damage. Targeting this pathway may represent a putative, novel, anticancer strategy in CCC.
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma.2016
Author(s)
Arakawa N, Kobayashi H, Yonemoto N, Masuishi Y, Ino Y, Shigetomi H, Furukawa N, Ohtake N, Miyagi Y, Hirahara F, Hirano H, Miyagi E.
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Journal Title
PLoS One.
Volume: 11
Issue: 10
Pages: e0165609-e0165609
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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