Bretschneider Nancy, Brand Heike, Miller Nicola, Lowery Aoife J, Kerin Michael J, Gannon Frank, Denger Stefanie
European Molecular Biology Laboratory, Heidelberg, Germany.
Cancer Res. 2008 Jan 1;68(1):106-14. doi: 10.1158/0008-5472.CAN-07-5647.
The focus of this study is on the expression and regulation of the estrogen-regulated breast cancer and salivary gland expression (BASE) gene that may function as a breast cancer marker. In MCF7 cells, BASE is repressed by estrogen in an estrogen receptor alpha (ER alpha)-dependent manner. Promoter analysis of the BASE gene led to the identification of a 2-kb upstream enhancer that harbors binding sites for ER alpha and FoxA1. The recruitment of both ER alpha and FoxA1 to this region was shown by chromatin immunoprecipitation analysis. Furthermore, mutation studies and knockdown experiments show a clear separation between gene expression mediated by FoxA1 and ER alpha-dependent gene regulation. Additionally, we provide information on BASE expression in human breast tumor samples.
本研究的重点是雌激素调节的乳腺癌和唾液腺表达(BASE)基因的表达与调控,该基因可能作为乳腺癌标志物发挥作用。在MCF7细胞中,BASE以雌激素受体α(ERα)依赖的方式被雌激素抑制。对BASE基因的启动子分析导致鉴定出一个2 kb的上游增强子,该增强子含有ERα和FoxA1的结合位点。染色质免疫沉淀分析表明ERα和FoxA1均募集到该区域。此外,突变研究和敲低实验表明FoxA1介导的基因表达与ERα依赖的基因调控之间存在明显区分。此外,我们提供了人类乳腺肿瘤样本中BASE表达的信息。