The observation that the effects of HER-2 overexpression on TGF-β responses in breast cancer cells is highly context dependent could be explained, for example, by a model in which two major branches of TGF-β responses exist: one that is inhibited by active ER signaling and the other that is inhibited by constitutive, high level ras/MAPK signaling (Fig. 7c,d). This evidence concerns the gene ESR1 and breast carcinoma.