2016 Fiscal Year Final Research Report
Pathogenesis of endometriosis and its malignant transformation.
Project/Area Number |
26293361
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Obstetrics and gynecology
|
Research Institution | Nara Medical University |
Principal Investigator |
|
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
|
Keywords | 子宮内膜症 / 卵巣癌 |
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.
|
Free Research Field |
婦人科腫瘍
|