DNA复制
生物
癌细胞
DNA复制因子CDT1
基因沉默
细胞生物学
分子生物学
真核细胞DNA复制
小干扰RNA
细胞凋亡
DNA
基因
癌症研究
核糖核酸
癌症
遗传学
作者
Daorong Feng,Zheng Jin Tu,Wenyan Wu,Chun Liang
出处
期刊:PubMed
日期:2003-11-01
卷期号:63 (21): 7356-64
被引量:37
摘要
DNA replication-initiation proteins are expressed in cancer cells, whereas some of these proteins are not expressed in nonproliferating normal cells. Therefore, replication-initiation proteins may present attractive targets for anticancer therapy. Using selected antisense oligodeoxynucleotides and small interfering RNA molecules targeted to the mRNA encoding the DNA replication-initiation proteins hCdc6p, hMcm2p, and hCdc45p, we show that the target genes could be effectively and specifically silenced and that, consequently, DNA replication and cell proliferation were inhibited in cultured human cells. In addition, silencing of these genes resulted in apoptosis in both p53-positive and -negative cancer cells but not in normal cells: cancer cells entered an abortive S-phase, whereas normal cells arrested mainly in G(1) phase. Our studies are the first to suggest that inhibiting the expression of selective replication-initiation proteins is a novel and effective anticancer strategy.
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