Samady Laila, Dennis Jonathan, Budhram-Mahadeo Vishwanie, Latchman David S
Medical Molecular Biology Unit, Institute of Child Health, University College London, London, UK.
Cancer Biol Ther. 2004 Mar;3(3):317-23. Epub 2004 Mar 10.
The Brn-3b POU family transcription factor has previously been shown to be over-expressed 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.
此前研究表明，Brn-3b POU家族转录因子在人类乳腺癌中过度表达，可提高人类乳腺癌细胞的生长速率并促进其非锚定依赖性生长，其作用至少部分是通过抑制抑癌基因BRCA-1的表达来实现的。在此，我们利用基因芯片来鉴定人类乳腺癌细胞中Brn-3b的其他几个靶点，包括细胞周期蛋白依赖性激酶4（CDK4）。具体而言，我们发现，在经处理以表达不同水平Brn-3b的乳腺癌细胞系以及人类乳腺癌活检样本中，CDK4 mRNA和蛋白水平与Brn-3b水平相关，并且Brn-3b可激活CDK4启动子。Brn-3b对生长调节性CDK4蛋白的作用提供了另一种机制，通过该机制Brn-3b可调节乳腺癌细胞生长，这表明它可通过激活以及抑制特定靶基因来做到这一点。
