Clinical and biological significance of Cdk10 in hepatocellular carcinoma

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• 作者：Xiang-yu Zhong^a ; ¹ ; Xiao-xue Xu^b ; ¹ ; Jian-hua Yu^a ; Gui-xing Jiang^a ; Yang Yu^c ; Sheng Tai^a ; Zhi-dong Wang^a ; Yun-fu Cui^a ; ^{yfcui777@yahoo.cn}
• 关键词：HCC ; Hepatocellular carcinoma ; HBV ; hepatitis B virus ; HCV ; hepatitis C virus ; AFP ; alpha fetoprotein ; Cdk ; Cyclin-dependent kinase ; LOH ; loss of heterozygosity ; pCMV6-CDK10 ; Cdk10-expressing plasmid ; MTT ; 3-(4 ; 5-dimethylthiazol-2-yl)-2 ; 5-diphenyltetrazol
• 刊名：Gene
• 出版年：2012
• 期刊代码：73_03781119
• 类别：bio
• 出版时间：25 April, 2012
• 卷：498
• 期：1
• 页码：68-74
• 文件大小：607 K

摘要

Cyclin-dependent kinase 10 (Cdk10) is a Cdc2-related kinase and plays an essential role in the progression from the G2 to M phase of the cell cycle. However, relative little is known about its expression pattern, clinical relevance, and biological function in hepatocellular carcinoma (HCC). In the present study, we investigated the mRNA and protein expression levels of Cdk10 in 127 pairs of HCC samples and adjacent nontumorous liver tissues and evaluated its clinical significance. Additionally, we assessed the effects of restoration of Cdk10 on cell proliferation and drug sensitivity in HCC cells. We showed that the Cdk10 mRNA and protein expression was markedly decreased in HCC samples compared to adjacent nontumorous liver tissues. Quantitative real-time polymerase chain reaction and immunohistochemical studies revealed that reduced Cdk10 expression was significantly associated with alpha-fetoprotein levels, tumor size, and tumor stage. Ectopic expression of Cdk10 reduced HCC cell proliferation, blocked the cell cycle at the G0-G1 phase, as well as inhibited cell migration and anchorage-independent growth. Additionally, Cdk10 overexpression enhanced the chemosensitivity of HCC cells to cisplatin and epidoxorubicin, two chemotherapeutic agents commonly used in HCC. These data collectively demonstrate that reduced Cdk10 expression is closely linked to HCC development and progression. Restoration of its expression may have therapeutic benefits in treating this malignancy.