SMAD3 and breast cancer: On the other hand, in-vivo data obtained by employing different mouse models of breast cancer [8,21,23,45] indicate that reducing TGF-β-signaling by impairing TβRII, TβRI kinase activity or Smad3-phosphorylation enhances development of the primary lesion but reduces metastasis whereas constitutive activation of TβRI has opposite effects.