雄激素依赖性前列腺癌细胞在其雄激素受体阻断后细胞周期基因表达的改变

The change in the expression of cell cycle related genes after the blockage of androgen receptor in the prostate cancer cells

目的 测定前列腺癌细胞系LNCaP在雄激素受体 (AR)阻断前后细胞周期基因表达的变化 ,探讨AR对细胞周期基因表达的影响。方法 在LNCaP细胞中加入氟他胺 ,然后抽提正常LNCaP细胞和加入氟他胺的LNCaP细胞中的mRNA制备cDNA探针 ,应用基因芯片技术观察两者细胞周期基因表达差异情况。结果 TRIZOL法提取细胞mRNA合格 ,从 8465个点位中筛选出差异表达基因共 3 2 6个 ,占 3 .93 % ;其中 97条下调 ,2 19条上调。其中与细胞周期明显相关的共有 8条基因 ,分别为CDC10、NRAS、BTG1、Wee1hu、CLK3、DKFZP5 64A12 2、CDKN1A和Btg2。其中尤以Btg1和CDKN1A表达水平较高。结论 雄激素受体在前列腺癌细胞中对细胞周期有着巨大影响。雄激素受体引起的前列腺癌细胞周期变化有多种基因参与。其中 ,CDKN1A基因和Btg1基因作用较大 ,并可能以p5 3非依赖途径作用于前列腺癌细胞。

Objective To elucidate the effect of androgen receptor on the expression of cell cycle related genes in prostate cancer cells by evaluating their changes after androgen receptor blockage.Methods Flutamide was added to LNCaP cells.The mRNA from both experiment group cells and the control group cells was extracted to make cDNA probes.The difference in the expression of cell cycle related genes was observed in both groups by genechips.Results The mRNA extracted by Trizol method was well qualified for genechips analysis.In all the 8?456 genes investigated,there were 326 differential expression genes,accounting for 3.93%.Among them,219 were up-regulated,while 97 down-regulated.There were 8 cell cycle related genes,including CDC10,NRAS,BTG1,Wee1 hu,CLK3,DKFZP564A122,CDKN1A,and Btg2.The expression of Btg1 and CDKN1A was increased distinctively.Conclusion Androgen receptor has a great impact on the cell cycle in the prostate cancer cells.The effect of androgen receptor on the cell cycle of prostate cancer cells is a multigene process.CDKN1A and Btg1 have great impacts on the cell cycle of prostate cancer cells,and may function on the cancer cells in a p53 independent pathway.