ATP modulation of mitogen activated protein kinases and intracellular Ca2+ in breast cancer (MCF-7) cells.
In the breast tumor cell line MCF-7, extracellular nucleotides induce transient elevations in intracellular calcium concentration ([Ca(2+)](i)). In this study we show that stimulation with ATP or UTP sensitizes MCF-7 cells to mechanical stress leading to an additional transient Ca(2+) influx. ATP> or =ATPgamma-S> or =UTP>>>ADP=ADPbeta-S elevate [Ca(2+)](i), proving the presence of P2Y(2)/P2Y(4) purinergic receptor subtypes. In addition, cell stimulation with ATP, ATPgamma-S or UTP but not ADPbeta-S induced the phosphorylation of ERK1/2, p38 and JNK1/2 mitogen activated protein kinases (MAPKs). The use of Gd(3+), La(3+) or a Ca(2+)-free medium, inhibited ATP-dependent stress activated Ca(2+) (SAC) influx, but had no effect on MAPK phosphorylation. ATP-induced activation of MAPKs was diminished by two PI-PLC inhibitors and an IP(3) receptor antagonist. These results evidence an ATP-sensitive SAC influx in MCF-7 cells and indicate that phosphorylation of MAPKs by ATP is dependent on PI-PLC/IP(3)/Ca(2+)(i) release but independent of SAC influx in these cells, differently to other cell types.
Scodelaro Bilbao
Paola
P
Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, (B8000ICN) Bahía Blanca, Argentina.
Boland
Ricardo
R
Russo de Boland
Ana
A
Santillán
Graciela
G
D000255:Adenosine Triphosphate / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008657:Metabolic Clearance Rate / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000255:Adenosine Triphosphate; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium