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

In this work, we studied the involvement of PKC and Src in the phosphorylation of ERK1/2, p38 and JNK1 MAPKs and in the modulation of ATF-1, c-Fos, c-Jun and Jun D transcription factors by ATP in MCF-7 breast cancer cells. RT-PCR studies and nucleotide sequence analysis confirmed first the expression of P2Y2- and P2Y4-receptor subtypes. The use of specific inhibitors and Src antisense oligonucleotides showed that PKC, but not Src, plays a role in the phosphorylation of MAPKs by ATP. ATP stimulated the expression of c-Fos and the phosphorylation c-Jun, Jun D and ATF-1. PKC and Src only participated in c-Fos induction and in ATF-1 phosphorylation. Pharmacological inhibition of MAPKs demonstrated that 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 transcription factors through PKC/MAPKs and PKC/Src pathways in MCF-7 cells.