Liu Weiwei, Wu Zhong, Guan Ming, Lu Yuan
Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Int J Urol. 2009 Mar;16(3):323-8. doi: 10.1111/j.1442-2042.2008.02199.x. Epub 2009 Jan 12.
To clarify molecular mechanisms involved in the action of pigment epithelium-derived factor (PEDF) in hormone insensitive prostate cancer cells.
Total ribonucleic acid from untreated and PEDF-treated cells was subjected to microarray analysis using BioStar 8464 microarray. Real-time polymerase chain reaction analysis was conducted to confirm the microarray data.
Twenty-seven out of 8464 genes were found altered in both cell lines. Common gene responses altered by PEDF were identified and included genes known to alter cell signaling as well as genes involved in catalytic activity, cell proliferation, angiogenesis and apoptosis. Real-time reverse transcription polymerase chain reaction, in accordance with the microarray analysis, indicated that PEDF treatment caused an upregulation in the mRNA expression level of stanniocalcin 2, brain-specific angiogenesis inhibitor 2 and growth arrest, DNA-damage-inducible, alpha, and downregulation in the messenger ribonucleic acid level of fibroblast growth factor 3, teratocarcinoma-derived growth factor, neuropilin1, and endothelial Per/ARNT/Sim domain protein1, respectively.
These findings demonstrate that PEDF administration causes significant changes in the gene expression of the prostate, providing insights into the potential role of PEDF in the treatment of prostate cancer.
阐明色素上皮衍生因子(PEDF)在激素不敏感前列腺癌细胞中的作用所涉及的分子机制。
使用BioStar 8464芯片对未处理及经PEDF处理的细胞的总核糖核酸进行芯片分析。进行实时聚合酶链反应分析以确认芯片数据。
在两种细胞系中发现8464个基因中有27个发生改变。确定了由PEDF改变的常见基因反应,包括已知可改变细胞信号传导的基因以及参与催化活性、细胞增殖、血管生成和凋亡的基因。实时逆转录聚合酶链反应与芯片分析一致,表明PEDF处理导致2型鲟钙蛋白、脑特异性血管生成抑制因子2以及生长停滞和DNA损伤诱导蛋白α的mRNA表达水平上调,以及成纤维细胞生长因子3、畸胎瘤衍生生长因子、神经纤毛蛋白1和内皮细胞Per/ARNT/Sim结构域蛋白1的信使核糖核酸水平下调。
这些发现表明,给予PEDF会导致前列腺基因表达发生显著变化,为PEDF在前列腺癌治疗中的潜在作用提供了见解。