p53负调控前列腺癌细胞中PC-1基因的表达

在前列腺癌进展中发生的PC-1基因表达失调和p53基因突变，提示这两个事件之间可能存在的联系.用依托泊苷处理前列腺癌LNCaP细胞后，PC-1蛋白的表达受抑制；瞬时转染分析表明野生型p53负调控PC-1启动子的转录活性；缺失突变分析将PC-1基因启动子上受p53负调控的区域定位在翻译起始位点上游757 bp～323 bp之间.缺失PC-1启动子上的雄激素受体反应元件并没有消除p53对其转录活性的抑制作用；无论p53是否存在，组蛋白去乙酰化酶抑制剂TSA处理LNCaP细胞后可以导致PC-1启动子转录活性升高.因此,p53和去乙酰化酶可以独立抑制PC-1启动子活性.这些研究结果表明,野生型p53负调控PC-1基因启动子的转录活性，而前列腺癌进展过程中p53突变可能和PC-1基因的表达失调有关.

p53 negatively regulated PC-1 expression in prostate cancer cells

Aberrant expression of PC-1 and the mutation of p53 in the development of prostate cancer hinted a possible link between these two events. PC-1 protein level decreased in the LNCaP cells which were treated with etoposide; transient transfection analyses revealed that wt-p53 negatively regulated the PC-1 promoter activity. Deletion and mutation analyses mapped the region of thePC-1 promoter which was negatively regulated by p53 between the 757 bp～323 bp which was upstream of the translation initiation site. Deleting the androgen receptor responsive element (ARE) from the PC-1 promoter did not abrogate the p53 mediated repression of the PC-1 promoter activity; Treatment of LNCaP cells with the histone deacetylase inhibitor, trichostatin A, resulted in an increase in the PC- present or not. Therefore, p53 and the histone deacetylase repressed the PC-1 promoter independently. These results indicate that wt-p53 negatively regulates the p53 mutations may play a role in the dysregulation of PC-1 in the development of prostate cancer.