SMAD4 and pancreatic neoplasm: In addition, previous studies have revealed that the TGFβ pathway is able to modify the oscillatory patterns of core clock genes from different tissues (33, 34, 35, 36), and other authors have reported a reduction in the expression of Bmal1 in heart tissue of Smad3 knockout mice (37) and a role for Smad4 in pancreatic cancer cells (38) increased transcriptional activity of several potential cis-regulatory elements after Smad3 overexpression.