CDK7 Is a Reliable Prognostic Factor and Novel Therapeutic Target in Epithelial Ovarian Cancer

Authors
Jeong-Won LeeJihye KimYoung-Jae ChoJi-Yoon RyuIlseon HwangHee Dong HanHyung Jun AhnWoo Young KimHanbyoul ChoJoon-Yong ChungStephen M. HewittJae-Hoon KimByoung-Gie KimDuk-Soo BaeChel Hun Choi
Department
Dept. of Pathology (병리학)
Issue Date
2020
Citation
Gynecologic oncology, Vol.156(1) : 211-221, 2020
ISSN
1095-6859
Abstract
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 (CDK7 High ) gradually increased from normal ovarian epithelium to EOC ( P < 0.001). Moreover, CDK7 High was associated with an advanced stage and high-grade histology ( P = 0.035 and P = 0.011, respectively) in EOC patients and had an independent prognostic significance in EOC recurrence ( P = 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. Conclusion: Mechanistic interrogation of CDK7 revealed that it is significantly associated with an aggressive phenotype of EOC, and it has independent prognostic power for EOC recurrence. Furthermore, CDK7 may be a potential therapeutic target for patients with EOC, whether platinum sensitive or resistant.
Keywords
Cyclin-dependent kinase 7Epithelial ovarian cancerPrognosisTHZ1Therapeutic target
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/42347
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
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Full Text
https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0090825819316257
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