Uridine triphosphate (Uridine 5'-triphosphate) increases proliferation of human cancerous pancreatic duct epithelial cells by activating P2Y2 receptor.

Incubation of PANC-1 cells with Uridine or MRS2768, a selective P2Y2 receptor agonist, resulted in a dose- and time-dependent increase of proliferation.The messenger RNA transcript and protein of P2Y2 receptor were expressed in PANC-1 cells.P2 receptor antagonist suramin and small interfering RNA against P2Y2 receptor significantly decreased the proliferative effect of Uridine and MRS2768.Activation of P2Y2 receptor by Uridine transduced to phospholipase C, inositol 1,4,5-triphosphate (IP3), and protein kinase C. Uridine triphosphate-induced proliferation was mediated by protein kinase D, Src-family tyrosine kinase, Ca/calmodulin-dependent protein kinase II, phosphatidylinositol 3-kinase (PI3K), Akt, and phospholipase D. Uridine triphosphate increased phosphorylation of Akt through protein kinase C, Src-family tyrosine kinase, Ca/calmodulin-dependent protein kinase II, and PI3K[1].

Proliferation was measured by immunoassay for bromodeoxyuridine incorporation into the pancreatic cell line PANC-1. Effect of UTP was assayed using selective P2 agonist and antagonist, small interfering RNA, intracellular signal inhibitors, and Western blot[1].