RB1 and breast carcinoma: Among this 20-gene set, were HER3 and one of its downstream target molecules GRB2 [33], hypoxia related molecule HIF1-alfa, MAPKinase cascade related protein CREBBP, cell cycle regulator RB1 and proliferation related genes CCNH, CDK7 and CDC25B. Since the brain is rich in neuregulin 1 [34,35] and this is a ligand for HER3, we hypothesized that the neuregulin-HER3 activation was important in allowing breast cancer cells to colonize the brain.