The Akt/protein kinase B-dependent anti-apoptotic pathway and the mitogen-activated protein kinase cascade are alternatively activated in human glioblastoma multiforme.
We investigated the activation of two important signal transduction pathways in human glioblastoma cells and found a constitutive phosphorylation of either Akt or mitogen-activated protein kinase (MAPK) under serum free conditions. In all but one cell line Wortmannin-sensitive activation of Akt could be attributed to the loss of functional PTEN protein. All cell lines with Akt activation exhibited only weak phosphorylation of the MAPK signal pathway, whereas those without constitutive Akt activation demonstrated high levels of phosphorylated MAPK under serum free conditions. Our data might indicate the presence of two functional subtypes of glioblastoma multiforme, since Akt and MAPK are involved in cellular survival and proliferation signalling, respectively.
Institut für Pathologie der Technischen, Universität München, Klinikum Rechts der Isar, Ismaninger Strasse 22, 81675, Munich, Germany. juergen.schlegel@lrz.tu-muenchen.de
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J
Schlegel
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Piontek
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Budde
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Neff
A
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Kraus
D017209:Apoptosis / Q000502:physiology*; D004789:Enzyme Activation; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009152:Mutagenicity Tests; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human