A recombinant adenovirus expressing p27(Kip1) induces cell cycle arrest and lass of cyclin-Cdk activity in human breast cancer cells
A recombinant adenovirus expressing p27(Kip1) induces cell cycle arrest and lass of cyclin-Cdk activity in human breast cancer cells
复制标题
DOI：
10.1038/sj.onc.1201064
复制
发表时间：
1997-05-15
期刊：
影响因子：
8
通讯作者：
Seth, P
中科院分区：
文献类型：
--
作者：
Craig, C;Wersto, R;Seth, P
为了阐明通用细胞周期蛋白激酶抑制因子p27(Kip1)调控人乳腺癌细胞周期进程的生化机制，构建了表达人p27的重组腺病毒Adp27。Adp27感染人乳腺癌细胞Mda-MB-231和MCF-7后，p27高表达，使多个细胞株中处于S期的细胞比例明显下降。比较Adp27和另一种表达相关通用细胞周期蛋白激酶抑制剂WAF1/Cip1的腺病毒载体(AdWAF1)的细胞毒作用，发现Adp27的毒性明显高于AdWAF1(最高可达56倍)，DNA直方图显示Adp27在较低病毒剂量时可导致G(1)/S阻滞。对Adp27感染后的细胞周期蛋白依赖性激酶活性的分析表明，与AdWAF1相比，在较低的病毒剂量下，CDK2和细胞周期蛋白B1-CDC2的活性降低，因此，Adp27对于生长调控的研究和需要生长抑制的基因治疗是潜在的有用的。
In order to elucidate the biochemical mechanisms by which the universal cyclin kinase inhibitor p27(Kip1) regulates cell cycle progression in human breast cancer cells, a recombinant adenovirus expressing human p27 was constructed (Adp27). Upon infection of human breast cancer cells MDA-MB-231 and MCF-7 with Adp27, a high level of p27 expression was observed, and this resulted in a marked decrease in the proportion of cells in S-phase, In multiple cell lines, comparison of the cytotoxicity of Adp27 with another adenovirus vector expressing the related universal cyclin kinase inhibitor WAF1/Cip1 (AdWAF1), showed Adp27 to be markedly more (up to 56-fold) toxic than AdWAF1, DNA histograms showed Adp27 to cause a G(1)/S arrest at lower viral doses than AdWAF1, Analysis of cyclin dependent kinase activity following Adp27 infections showed decreased Cdk2 and cyclin B1-Cdc2 activity at lower viral doses when compared with AdWAF1, Adp27 is therefore potentially useful for studies of growth regulation and for gene therapy when growth inhibition is desired.