Figure 2.

Interaction of BRCA1 and E-ER and their regulation of mammary epithelial cell differentiation. The differentiation of mammary epithelial progenitor cells is restricted by several key regulators such as SLUG and SOX9. BRCA1 may contribute to the cell differentiation by repressing SLUG in both multi-potent progenitor cells and committed progenitor cells. However, E-ER signaling may promote cell proliferation and increase these stem cell related factors, which start to turn on the related gene transcription programs and promote cell de-differentiation. In normal condition, the balance between BRCA1 and E-ER is important to maintain a homeostatic SLUG level and ensures the appropriate differentiation program. Under BRCA1 deficiency condition, the cells start to gain stem cell features. When this process is coupled with increased cellular damages, such as ROS related damages, the opportunity of oncogenic transformation increases.