期刊
ONCOGENE
卷 26, 期 7, 页码 1003-1012出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1209864
关键词
stathmin; cell-cycle arrest; mitosis; apoptosis; breast cancer
资金
- NCI NIH HHS [CA 78695, CA 72720] Funding Source: Medline
Cancers harboring dominant-negative p53 mutations are often aggressive and difficult to treat. Direct attempts to restore wild-type p53 function have produced little clinical benefit. We investigated whether targeting a p53-target gene could induce certain tumor-suppressor characteristics. We found that inhibition of stathmin, a microtubule regulator that can be transcriptionally repressed by wildtype p53, restored certain wild-type functions to cancer cells with mutant p53. Silencing of stathmin by small interfering RNA ( siRNA) in mutant p53 cell lines lowered expression to that observed following activation of wildtype p53 by DNA damage in wild-type p53 cell lines. siRNA-induced repression of stathmin decreased cell proliferation, viability and clonogenicity in mutant p53 cell lines. Furthermore, knockdown of stathmin partially restored cell-cycle regulation and activation of apoptosis. Therefore, targeting stathmin, a gene product that is overexpressed in the presence of mutant p53, may represent a novel approach to treating cancers with aberrant p53 function.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据