ATP modulates transcription factors through P2Y2 and P2Y4 receptors via PKC/MAPKs and PKC/Src pathways in MCF-7 cells

Abstract

In this work, we studied the involvement of PKC and Src in the phosphorylation of ERK1/2, p38 and JNK1MAPKs and in the modulation of ATF-1, c-Fos, c-Jun and Jun D transcription factors by ATP in MCF-7breast cancer cells. RT-PCR studies and nucleotide sequence analysis confirmed first the expression ofP2Y2- and P2Y4-receptor subtypes. The use of specific inhibitors and Src antisense oligonucleotidesshowed that PKC, but not Src, plays a role in the phosphorylation of MAPKs by ATP. ATP stimulatedthe expression of c-Fos and the phosphorylation c-Jun, Jun D and ATF-1. PKC and Src only participatedin c-Fos induction and in ATF-1 phosphorylation. Pharmacological inhibition of MAPKs demonstratedthat c-Fos induction and phosphorylation of c-Jun and Jun D, but not of ATF-1, depend on MAPK activation.These results suggest that stimulation of P2Y2 and P2Y4 receptors by ATP modulates transcriptionfactors through PKC/MAPKs and PKC/Src pathways in MCF-7 cells.