期刊
ONCOGENE
卷 28, 期 25, 页码 2406-2418出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2009.81
关键词
breast cancer; invasion; PI3K; PIK3CA; uPA; YB-1
资金
- National Cancer Institute of Canada (SED) [RO1 CA114017-01A1]
- Canadian Institute of Health Research
- Canadian Breast Cancer Research Alliance IDEA
- Canadian Institute of Health Research MD/PhD
- Michael Smith Foundation for Health Research Studentships.
PIK3CA, which codes for the p110 alpha catalytic subunit of phosphatidylinositol-3-kinase (PI3K), is implicated as an oncogene. Despite importance of PIK3CA in cancer, little is known about what drives up its expression in tumor cells. We recently characterized the PIK3CA promoter and reported that it is transcriptionally silenced by the tumor suppressor protein p53. In the present study, we demonstrate that PIK3CA can be induced by the oncogenic transcription factor Y-box binding protein-1(YB-1). Three YB-1-responsive elements were identified on the PIK3CA promoter using chromatin immunoprecipitation and electrophoretic mobility shift assays. Interestingly, silencing YB-1 with siRNA in models of basal-like breast cancer decreased p110 alpha protein levels regardless of whether PIK3CA was wild type, amplified or mutated. This decrease in p110 alpha led to a reduction in PI3K activity and the downstream signaling primarily through p90 ribosomal S6 kinase and S6 ribosomal protein. Disruption in PIK3CA-dependent signaling suppressed cellular invasion correlative with loss of urokinase plasminogen activator (uPA). Similarly, silencing YB-1 suppressed invasion and uPA production however this was reversible through the introduction of constitutively active PIK3CA. In conclusion, YB-1 is the first reported oncogene to induce the expression of PIK3CA through transcriptional control of its promoter. Oncogene (2009) 28, 2406-2418; doi:10.1038/onc.2009.81; published online 11 May 2009
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