SMAD3 and neoplasm: To elucidate the mechanistic relationship between the TLR overexpression and the increased tumor growth in mice with VD deficiency and Smad3 deletion-induced impairment of TGF-β signaling, the DEN-injected wild type and Smad3+/− mice were fed with either high or low VD food for 4 months beginning in the 8th month of life (Fig. 1a).