Activation of CDK4 gene expression in human breast cancer cells by the Brn-3b POU family transcription factor

被引:29
|
作者
Samady, L
Dennis, J
Budhram-Mahadeo, V
Latchman, DS [1 ]
机构
[1] Univ London Birkbeck Coll, London WC1E 7HX, England
[2] UCL, Inst Child Hlth, Med Mol Biol Unit, London, England
关键词
breast cancer; cDNA microarray; expression profiling; Brn-3b transcription factor; CDK4;
D O I
10.4161/cbt.3.3.698
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The Brn-3b POU family transcription factor has previously been shown to be overexpressed in human breast cancer and to enhance the growth rate and anchorage independent growth of human breast cancer cells, acting at least in part by inhibiting the expression of the BRCA-1 anti-oncogene. Here we have used gene arrays to identify several other targets for Brn-3b in human breast cancer cells, including cyclin-dependent kinase 4 (CDK4). In particular, we show that levels of CDK4 mRNA and protein correlate with the levels of Brn-3b in breast cancer cell lines manipulated to express different levels of Brn-3b and in human breast cancer biopsies and that Brn-3b can activate the CDK4 promoter. The effect of Brn-3b on the growth regulatory CDK4 protein provides a further mechanism by which Brn-3b can regulate breast cancer cell growth and indicates that it can do this by activating as well as repressing specific target genes.
引用
收藏
页码:317 / 323
页数:7
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