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 P2Y(2)- and P2Y(4)-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 P2Y(2) and P2Y(4) receptors by ATP modulates transcription factors through PKC/MAPKs and PKC/Src pathways in MCF-7 cells.
Scodelaro Bilbao
Paola
P
Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, Bahía Blanca, Argentina.
Boland
Ricardo
R
Santillán
Graciela
G
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058473:Receptors, Purinergic P2Y2; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000502:physiology*
D017931:DNA Primers; C546385:P2RY2 protein, human; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D014157:Transcription Factors; C104749:purinoceptor P2Y4; D000255:Adenosine Triphosphate; D016392:Proto-Oncogene Proteins pp60(c-src); D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases