Li Zhengyu, Zhao Xia, Bai Shujun, Wang Zhi, Chen Lijuan, Wei Yuquan, Huang Canhua
Department of Gynecology and Obstetrics, West China Second [corrected] Hospital, Sichuan University, Chengdu 610041, China.
Mol Cell Proteomics. 2008 Oct;7(10):1810-23. doi: 10.1074/mcp.M700544-MCP200. Epub 2008 Apr 17.
Endometrial carcinoma is one of the most common malignancies of the female genital tract, and there is an urgent need for discovery of novel factors for prognostic assessment and therapeutic targets to endometrial carcinoma. Herein a two-dimensional gel electrophoresis and MALDI-Q-TOF MS/MS-based proteomics approach was used to identify differentially expressed proteins in endometrial carcinoma. Of the 99 proteins identified, cyclophilin A was one of the most significantly altered proteins, and its overexpression was confirmed using RT-PCR and Western blot analyses. Immunohistochemistry suggested a link between cyclophilin A expression and poor differentiation and decreased survival (p < 0.01). Knockdown of cyclophilin A expression by RNA interference led to the significant suppression of the cell growth and the induction of apoptosis in endometrial carcinoma HEC-1-B cells in vitro (p < 0.01) and the inhibition of tumor growth in vivo (p < 0.01). These data suggest that cyclophilin A may serve as a novel prognostic factor and possibly an attractive therapeutic target for endometrial carcinoma.
子宫内膜癌是女性生殖道最常见的恶性肿瘤之一,迫切需要发现新的因素用于子宫内膜癌的预后评估和治疗靶点。在此,采用二维凝胶电泳和基于基质辅助激光解吸电离飞行时间串联质谱(MALDI-Q-TOF MS/MS)的蛋白质组学方法来鉴定子宫内膜癌中差异表达的蛋白质。在鉴定出的99种蛋白质中,亲环素A是变化最显著的蛋白质之一,通过逆转录-聚合酶链反应(RT-PCR)和蛋白质免疫印迹分析证实了其过表达。免疫组织化学表明亲环素A表达与低分化及生存率降低之间存在关联(p<0.01)。通过RNA干扰敲低亲环素A的表达导致体外子宫内膜癌HEC-1-B细胞的细胞生长显著受抑并诱导细胞凋亡(p<0.01),以及体内肿瘤生长受抑(p<0.01)。这些数据表明亲环素A可能作为一种新的预后因素,并且可能是子宫内膜癌一个有吸引力的治疗靶点。