As tumor suppressor factors, TGFβRII or SMAD4 knockout significantly accelerated progression of malignant tumors; examples include APC inactivation in intestinal polyps, PyMT-induced breast cancer, and pancreatic injury induced by Kras (Biswas et al., 2004; Forrester et al., 2005; Ijichi et al., 2006; Munoz et al., 2006). Here, SMAD4 is linked to breast cancer.