Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, BCM600, Houston, TX 77030, USA.
Breast Cancer Res. 2011 Apr 20;13(2):307. doi: 10.1186/bcr2849.
Estrogen receptor α (ER) is a major driver of breast cancer and the target of endocrine therapy. Full disclosure of the cofactors regulating ER interactions with chromatin and its transcriptional regulatory activity is still elusive. Novel genome-wide profiling tools have mapped ER binding events in breast cancer cells and delineated cofactors important in ER activity. Among these, the Forkhead protein FOXA1 is emerging as a key factor dictating global chromatin structure and the transcriptional function of ER in breast and non-breast cancer cells. The significance of FOXA1 in the chromatin interactions and transcriptional regulation of both estrogen- and tamoxifen-bound ER, and in supporting tamoxifen-resistant cell growth, may impact current endocrine therapies.
雌激素受体 α（ER）是乳腺癌的主要驱动因素，也是内分泌治疗的靶点。调节 ER 与染色质相互作用及其转录调控活性的协同因子的全面揭示仍难以捉摸。新型全基因组分析工具已经绘制了乳腺癌细胞中 ER 结合事件，并描绘了 ER 活性中的重要协同因子。在这些协同因子中，叉头框蛋白 FOXA1 作为决定全局染色质结构和 ER 在乳腺和非乳腺癌细胞中转录功能的关键因素而崭露头角。FOXA1 在雌激素和他莫昔芬结合的 ER 的染色质相互作用和转录调控中的意义，以及在支持他莫昔芬耐药细胞生长中的意义，可能会影响当前的内分泌治疗。
