Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Gene. 2012 Apr 25;498(1):68-74. doi: 10.1016/j.gene.2012.01.022. Epub 2012 Feb 1.
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.
周期蛋白依赖性激酶 10（Cdk10）是一种与 Cdc2 相关的激酶，在细胞周期的 G2 期到 M 期进展中发挥着重要作用。然而，人们对其在肝细胞癌（HCC）中的表达模式、临床相关性和生物学功能知之甚少。在本研究中，我们研究了 127 对 HCC 样本及其相邻非肿瘤性肝组织中 Cdk10 的 mRNA 和蛋白表达水平，并评估了其临床意义。此外，我们评估了恢复 Cdk10 对 HCC 细胞增殖和药物敏感性的影响。我们发现，与相邻非肿瘤性肝组织相比，Cdk10 的 mRNA 和蛋白表达在 HCC 样本中明显降低。定量实时聚合酶链反应和免疫组织化学研究表明，Cdk10 表达降低与甲胎蛋白水平、肿瘤大小和肿瘤分期显著相关。Cdk10 的异位表达降低了 HCC 细胞的增殖能力，将细胞周期阻滞在 G0-G1 期，并抑制了细胞迁移和无锚定依赖性生长。此外，Cdk10 的过表达增强了 HCC 细胞对顺铂和表阿霉素这两种常用于 HCC 治疗的化疗药物的敏感性。这些数据表明，Cdk10 表达的降低与 HCC 的发生和发展密切相关。恢复其表达可能对治疗这种恶性肿瘤具有治疗益处。
