title: Signal transduction pathways associated with ATP-induced proliferation of colon adenocarcinoma cells.
abstract: BACKGROUND
  In previous work, we have demonstrated that extracellular adenosine 5'-triphosphate (ATP) acts on intestinal Caco-2 cell P2Y receptors promoting a rapid increase in the phosphorylation of ERK1/2, p46 JNK and p38 MAP kinases (MAPKs).
  
  
  RESULTS
  In this study, we investigated whether the extracellular ATP-P2Y receptor signalling pathways were required for the proliferation of Caco-2 cells. Confocal microscopy and immunobloting studies showed that ERK1/2 and JNK translocate into the nucleus of the cells stimulated by ATP, where they participate, together with p38 MAPK, in the phosphorylation of JunD, ATF-1 and ATF-2 transcription factors. In addition, ATP through the activation of MAPKs induces the expression of the immediate early genes products of the Jun family, c-Fos and MAP kinase phosphatase-1 (MKP-1). Moreover, ERK1/2 and p38 MAPK are involved in the phosphorylation of MKP-1 in Caco-2 cells. Of physiological significance, in agreement with the mitogenic role of the MAPK cascade, ATP increased Caco-2 cell proliferation, and this effect was blocked by UO126, SB203580 and SP600125, the specific inhibitors of ERK1/2, p38 MAPK and JNK1/2, respectively.
  
  
  CONCLUSIONS
  Extracellular ATP induces proliferation of Caco-2 human colonic cancer cells by activating MAPK cascades and modulation of transcription factors.
  
  
  CONCLUSIONS
  These findings and identification of the specific P2Y subtype receptors involved in the mitogenic effect of ATP on Caco-2 cells might be relevant for understanding tumor cell development, resistance to treatment regimens and the design of new therapeutic strategies.
authors.affiliation: Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, 8000 Bahía Blanca, Argentina.
authors.forename: Natalia
authors.initials: N
authors.lastname: Buzzi
authors.forename: Ricardo
authors.initials: R
authors.lastname: Boland
authors.forename: Ana
authors.initials: A
authors.lastname: Russo de Boland
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D054638:Dual Specificity Phosphatase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D014157:Transcription Factors; D000255:Adenosine Triphosphate; D048049:Extracellular Signal-Regulated MAP Kinases; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1