摘要目的 探讨核干因子(NS)基因在前列腺癌恶性增殖中的作用机制.方法 采用表达谱基因芯片技术,分析前列腺癌PC-3细胞NS基因表达下调后全基因组表达谱的变化,筛选与NS相互作用的差异表达基因及信号通路.采用实时荧光定量聚合酶链反应对重要的差异表达基因进行验证.结果 共筛选出219个差异表达的基因,这些基因涉及到细胞周期、细胞增殖、信号转导、细胞凋亡和细胞分化等多个方面.NS基因表达下调后主要引起周期素依赖激酶4抑制因子(INK4)家族基因(p15、p16和p18)的上调,以及cyclin D1和HDACI基因的下调,其主要作用点位于CDK4/6-cyclinD和pRb-E2F1复合体上.结论 在前列腺癌PC-3细胞中,NS基因可能主要通过抑制p15、p16和p18等INK4家族的肿瘤抑制基因的表达,从而促进肿瘤的发生和发展;NS基因是细胞周期G1/S期检查点的重要调控因子.

abstractsObjective To screen the genes and possible signal transduction pathways involved in the mechanism of nucleostemin (NS) in the proliferation of prostate cancer. Methods Oligonucleotide DNA microarray was used to screen the genome changes after knocking-down expression of NS in PC-3 cells and quantitative real-time PCR was used to further confirm the important differentially expressed genes. Results 219 differentially expressed genes were found and theses genes were involved in cell cycle, cell proliferation, signal transduction, cell apoptosis and cell differentiation, etc. INK4 family genes (p15, p16, p18) were up-regulated and cyclin D1, HDAC1 were down-regulated, the main action points were CDK4/6-cyclin D and pRb-E2FI complexes. Conclusion NS may promote the progression of prostate cancer by inhibiting the expression of p15, p16, and p18 in PC-3 cells. NS is an important G1/S checkpoint regulator and its regulatory activity has been certified at gene level.