Department of Oncology, Department of Breast Surgery, Breast Cancer Institute, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Acta Biochim Biophys Sin (Shanghai). 2013 Mar;45(3):179-87. doi: 10.1093/abbs/gmt001. Epub 2013 Jan 24.
BRCA1 is closely related to the pathogenesis of breast cancer. The activity of BRCA1 promoter is regulated by transcriptional factors. The transcription factor Nrf2 (Nuclear factor-erythroid-2p45-related factor 2) is a potent transcriptional activator and plays a central role in inducible expression of many cytoprotective genes. In this report, we found that over-expression of Nrf2 stimulated BRCA1 expression, knockdown of Nrf2 attenuated BRCA1 expression. Nrf2 also interacted with CBP and p300 to form an active transcription complex, which could bind to the ARE (antioxidant response element) site on the BRCA1 promoter and activate its transcription by inducing histone acetylation. Our finding could lead to a better understanding of the development of breast cancer.
BRCA1 与乳腺癌的发病机制密切相关。BRCA1 启动子的活性受转录因子调控。转录因子 Nrf2(核因子-红细胞 2p45 相关因子 2)是一种有效的转录激活因子,在许多细胞保护基因的诱导表达中发挥核心作用。在本报告中,我们发现 Nrf2 的过表达刺激了 BRCA1 的表达,Nrf2 的敲低则减弱了 BRCA1 的表达。Nrf2 还与 CBP 和 p300 相互作用形成一个活跃的转录复合物,该复合物可以结合到 BRCA1 启动子上的 ARE(抗氧化反应元件)位点,并通过诱导组蛋白乙酰化来激活其转录。我们的发现可以帮助更好地理解乳腺癌的发生发展。