The estrogen receptor/GATA3/FOXA1 transcriptional network: lessons learned from breast cancer

Cellular identity and physiologic function in mammary epithelial cells and in many breast cancers flow from the action of a network of master transcriptional regulators including estrogen receptor alpha, GATA3, and FOXA1. The last decade has seen the completion of multiple large sequencing projects focusing on breast cancer. These massive compendia of sequence data have provided a wealth of new information linking mutation in these transcription factors to alterations in tumor biology and transcriptional program. The emerging details on mutation in cancer, and direct experimental exploration of hypotheses based on it, are now providing a wealth of new information on the roles played by estrogen receptor alpha, GATA3, and FOXA1 in regulating gene transcription and how their combined action contributes to a network shaping cell function in both physiologic and disease states.