Activation of CDK4 gene expression in human breast cancer cells by the Brn-3b POU family transcription factor
Activation of CDK4 gene expression in human breast cancer cells by the Brn-3b POU family transcription factor
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DOI：
10.4161/cbt.3.3.698
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发表时间：
2004-03-01
影响因子：
3.6
通讯作者：
Latchman, DS
中科院分区：
文献类型：
--
作者：
Samady, L;Dennis, J;Latchman, DS
Brn-3b POU家族转录因子先前已显示在人乳腺癌中过表达，并增强人乳腺癌细胞的生长速率和锚定非依赖性生长，至少部分通过抑制BRCA-1抗癌基因的表达起作用。在这里，我们已经使用基因阵列来确定其他几个目标的Brn-3b在人类乳腺癌细胞，包括细胞周期蛋白依赖性激酶4（CDK 4）。特别是，我们表明，CDK 4 mRNA和蛋白质的水平与乳腺癌细胞系中的Brn-3b的水平相关，这些细胞系被操纵以表达不同水平的Brn-3b，并且在人乳腺癌活检中，Brn-3b可以激活CDK 4启动子。Brn-3b对生长调节CDK 4蛋白的作用提供了Brn-3b可以调节乳腺癌细胞生长的进一步机制，并表明它可以通过激活和抑制特定靶基因来实现这一点。
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.