Yu Xiu-Yue, Zhang Zhe, Zhang Guo-Jun, Guo Kun-Feng, Kong Chui-Ze
Department of Urology, The First Hospital of China Medical University, Shenyang, China.
Asian Pac J Cancer Prev. 2012;13(3):931-5. doi: 10.7314/apjcp.2012.13.3.931.
Cdc25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. However, the role of Cdc25B in renal cell carcinomas remains unknown. To shed light on influence on renal cell carcinogenesis and subsequent progression, Cdc25B expression was examined by real-time RT-PCR and western blotting in renal cell carcinoma and normal tissues. 65 kDa Cdc25B expression was higher in carcinomas than in the adjacent normal tissues (P<0.05), positive correlations being noted with clinical stage and histopathologic grade (P<0.05). To additionally investigate the role of Cdc25B alteration in the development of renal cell carcinoma, Cdc25B siRNA was used to knockdown the expression of Cdc25B. Down-regulation resulted in slower growth, more G2/M cells, weaker capacity for migration and invasion, and induction of apoptosis in 769-P transfectants. Reduction of 14-3-3 protein expression appeared related to Cdc25B knockdown. These findings suggest an important role of Cdc25B in renal cell carcinoma development and provide a rationale for investigation of Cdc2B-based gene therapy.
细胞周期蛋白磷酸酶25(Cdc25)是细胞周期的重要调节因子。在许多肿瘤中检测到它们的异常表达,这表明它们的失调与恶性转化有关。然而,Cdc25B在肾细胞癌中的作用仍然未知。为了阐明其对肾细胞癌发生及后续进展的影响,通过实时逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹法检测了肾细胞癌组织和正常组织中Cdc25B的表达。结果显示,癌组织中65 kDa的Cdc25B表达高于相邻正常组织(P<0.05),且与临床分期和组织病理学分级呈正相关(P<0.05)。为了进一步研究Cdc25B改变在肾细胞癌发生中的作用,使用Cdc25B小干扰RNA(siRNA)敲低Cdc25B的表达。下调Cdc25B导致769-P转染细胞生长减慢、G2/M期细胞增多、迁移和侵袭能力减弱以及诱导细胞凋亡。14-3-3蛋白表达的降低似乎与Cdc25B的敲低有关。这些发现表明Cdc25B在肾细胞癌发生中起重要作用,并为基于Cdc2B的基因治疗研究提供了理论依据。