CDK7 is a reliable prognostic factor and novel therapeutic target in epithelial ovarian cancer
- CDK7 is a reliable prognostic factor and novel therapeutic target in epithelial ovarian cancer
- 안형준; 김지혜; 조영재; 류지윤; 황일선; 한희동; 김우영; 조한별; 정준용; 스테펜 헤위트; 김재훈; 김병기; 배덕수; 최철헌; 이정원
- CDK7; prognostic factor; therapeutic target; ovarian cancer; anticancer effect
- Issue Date
- Gynecologic oncology
- VOL 156-221
- Objective: Cyclin-dependent kinase 7 (CDK7) engages tumor growth by acting as a direct link between
the regulation of transcription and the cell cycle. Here, we investigated the clinical significance of CDK7
expression and its potential as a therapeutic target in epithelial ovarian cancer (EOC).
Methods: CDK7 expression was examined in 436 ovarian tissues including normal to metastatic ovarian
tumors using immunohistochemistry, and its clinical implications were analyzed. Furthermore, we
performed in vitro and in vivo experiments using CDK7 siRNA or a covalent CDK7 inhibitor (THZ1) to
elucidate the effect of CDK7 inhibition on tumorigenesis in EOC cells.
Results: The patient incidence of high CDK7 expression (CDK7High) gradually increased from normal
ovarian epithelium to EOC (P < 0.001). Moreover, CDK7High was associated with an advanced stage and
high-grade histology (P ¼ 0.035 and P ¼ 0.011, respectively) in EOC patients and had an independent
prognostic significance in EOC recurrence (P ¼ 0.034). CDK7 inhibition with siRNA or THZ1 decreased cell
proliferation and migration, and increased apoptosis in EOC cells, and this anti-cancer mechanism is
caused by G0/G1 cell cycle arrest. In in vivo therapeutic experiments using cell-line xenograft and PDX
models, CDK7 inhibition significantly decreased the tumor weight, which was mediated by cell proliferation
- Appears in Collections:
- KIST Publication > Article
- Files in This Item:
There are no files associated with this item.
- RIS (EndNote)
- XLS (Excel)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.