p53负调控前列腺癌细胞中PC-1基因的表达  

p53 Negatively Regulates PC-1 Expression in Prostate Cancer Cells

作　　者：王健[1] 张惠[1] 周建光[1] 黄翠芬[1] 

机构地区：[1]军事医学科学院生物工程研究所,北京100850

出　　处：《中国生物化学与分子生物学报》2006年第9期711-715,共5页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金资助(No.30070296)~~

摘　　要：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,PC1蛋白的表达受抑制;瞬时转染分析表明野生型p53负调控PC1启动子的转录活性;缺失突变分析将PC1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757bp～323bp之间.缺失PC1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PC1启动子转录活性升高.因此,p53和去乙酰化酶可以独立抑制PC1启动子活性.这些研究结果表明,野生型p53负调控PC1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.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-1 promoter activity whether p53 was present or not. Therefore, p53 and the histone deacetylase repressed the PC-1 promoter independently. These results indicate that wt-p53 negatively regulates the PC-1 promoter activity and p53 mutations may play a role in the dysregulation of PC-1 in the development of prostate cancer.

关 键 词：PC-1 P53 负调控 

分 类 号：Q78[生物学—分子生物学]