title: ERK, PKC and PI3K/Akt pathways mediate extracellular ATP and adenosine-induced proliferation of U138-MG human glioma cell line.
abstract: OBJECTIVE
  Extracellular nucleotides and nucleosides induce proliferation in a set of human glioma cell lines. In this study we investigate the signal transduction pathways involved in ATP and adenosine-mediated proliferation in U138-MG human glioma cells.
  
  
  METHODS
  Cell proliferation was accessed through [(3)H]thymidine incorporation, cell counting and flow cytometry. Protein phosphorylation was detected through Western blotting.
  
  
  RESULTS
  ATP or adenosine (100 microM) induced extracellular signal-regulated protein kinase (ERK), Akt and GSK3beta phosphorylation. The increase in [(3)H]thymidine incorporation induced by ATP or adenosine was decreased when cells were incubated with LY 294002 (by +/-90%), GF 109203X (by +/-76%) or PD 098059 (by +/-63%). The increase in cell numbers with ATP or adenosine was less after a 48-hour treatment of cells with ATP or adenosine plus GF 109203X (by +/-66%) or LY 294002 (by +/-83%). Percentage of cells in S phase was decreased in cells treated with LY 294002 plus ATP when compared to ATP- treated cells.
  
  
  CONCLUSIONS
  Stimulation of purinergic receptors in U138-MG cells leads to cell proliferation mediated by PI3K/Akt, ERK and PKC signaling. It may be clinically important for pharmacological intervention in gliomas to associate purinergic receptor antagonists and signal transduction pathways blockers.
authors.affiliation: Departamentos de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Jacques-Silva
authors.forename: Andressa
authors.initials: A
authors.lastname: Bernardi
authors.forename: Richard
authors.initials: R
authors.lastname: Rodnight
authors.forename: Guido
authors.initials: G
authors.lastname: Lenz
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005434:Flow Cytometry; D005910:Glioma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000241:Adenosine; D000255:Adenosine Triphosphate; D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494918:AKT1 protein, human; C000605506:GSK3B protein, human