ERK, PKC and PI3K/Akt Pathways Mediate Extracellular ATP and Adenosine-Induced Proliferation of U138-MG Human Glioma Cell LineJacques-Silva M.C.a · Bernardi A.a · Rodnight R.a · Lenz G.b
Departamentos deaBioquímica and bBiofísica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
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 [3H]thymidine incorporation, cell counting and flow cytometry. Protein phosphorylation was detected through Western blotting. Results: ATP or adenosine (100 µM) induced extracellular signal-regulated protein kinase (ERK), Akt and GSK3β phosphorylation. The increase in [3H]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. Conclusion: 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.
© 2004 S. Karger AG, Basel
Received: December 12, 2003
Accepted after revision: May 15, 2004
Number of Print Pages : 10
Number of Figures : 4, Number of Tables : 0, Number of References : 73
Oncology (International Journal of Cancer Research and Treatment)
Vol. 67, No. 5-6, Year 2004 (Cover Date: Released January 2005)
Journal Editor: D.L. Trump, Buffalo, N.Y.
ISSN: 0030–2414 (print), 1423–0232 (Online)
For additional information: http://www.karger.com/ocl