In contrast, our present data have clearly shown that metformin up-regulated DR5 in p53-mutant pancreatic cancer PANC-1 (Fig 4), AsPC-1 and MIA PaCa-2 cells (S6 Fig), indicating that metformin up-regulates DR5 expression in a p53-independent manner. The gene discussed is TP53; the disease is familial pancreatic carcinoma.