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
안형준김지혜조영재류지윤황일선한희동김우영조한별정준용스테펜 헤위트김재훈김병기배덕수최철헌이정원
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 and apoptosis.
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