Accumulation of cytoplasmic Cdk1 is associated with cancer growth and survival rate in epithelial ovarian cancer

被引:78
|
作者
Yang, Wookyeom [1 ,2 ]
Cho, Hanbyoul [1 ,2 ]
Shin, Ha-Yeon [1 ,2 ]
Chung, Joon-Yong [3 ]
Kang, Eun Suk [4 ]
Lee, Eun-Ju [1 ,2 ]
Kim, Jae-Hoon [1 ,2 ]
机构
[1] Yonsei Univ, Coll Med, Dept Obstet & Gynecol, Gangnam Severance Hosp, Seoul, South Korea
[2] Yonsei Univ, Coll Med, Inst Womens Life Med Sci, Seoul, South Korea
[3] NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA
[4] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Lab Med, Seoul, South Korea
基金
新加坡国家研究基金会;
关键词
Cdk1; cytoplasmic accumulation; epithelial ovarian cancer; RO-3306; PREDICTS POOR-PROGNOSIS; KINASE; CDK1; CELL-CYCLE; BRCA1; MUTATION; BREAST-CANCER; EXPRESSION; PROLIFERATION; PHOSPHORYLATION; OVEREXPRESSION; APOPTOSIS;
D O I
10.18632/oncotarget.10373
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cyclin dependent kinase 1 (Cdk1) have previously reported correlation with cancer growth and a key regulator for cell cycle. Mostly, Cdk1' s function of nucleus for cell cycle is well known to be associated with cancer, but cytoplasmic Cdk1's traits are not clearly identified, yet. We revealed that tissue microarray blocks of epithelial ovarian cancer (n = 249) showed increased level of cytoplasmic Cdk1 (p < 0.001), but not in nucleus (p = 0.192) of histologic cell type independently. On survival analysis, Cdk1 overexpression conferred a significantly worse prognosis in 5-year overall survival (Log-rank p = 0.028, Hazard ratio = 2.016, 95% CI = 1.097 to 4.635). Also, the expression of Cdk1 was increased in ovarian cancer cell lines and Gene Expression Omnibus datasets. When the expression and activity of Cdk1 were inhibited by si-Cdk1 or RO-3306 which is a potent Cdk1 inhibitor, the growth of ovarian cancer was diminished. Moreover, combined treatment with RO-3306 and cisplatin in ovarian cancer significantly elevated anti-cancer effects than single-agent treatment. In conclusion, cytoplasmic Cdk1 expression which was elevated in ovarian cancer predicts a poor overall survival. The inhibition of Cdk1 expression and activity reduced ovarian cancer growth.
引用
收藏
页码:49481 / 49497
页数:17
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