SMAD4 and familial pancreatic carcinoma: In addition, the inactivation of down-stream targets of TGF-β induced signalling pathways, such as Smad4 which is mutated or deleted in a high percentage of pancreatic cancers, may lead to a subsequent induction of TGF-β1 expression in pancreatic cancers (Hahn and Schmiegel, 1998).