Activation of the anti-apoptotic Akt/protein kinase B pathway in human malignant gliomas in vivo.
In the present study we investigated two important signal transduction pathways in glioma biopsies. By Western analysis we found an overexpression of the epidermal growth factor receptor in 10 out of 27 (37%) glioblastoma multiforme (GBM), but not in astrocytomas WHO II/III which demonstrated only weak or absent expression. Only two GBM (8%) but none of the astrocytomas WHO II/III exhibited loss of PTEN expression. Activation of Akt/protein kinase B showed a close correlation with EGF receptor overexpression in human malignant gliomas since 6 out of 7 GBMs with high degrees of protein kinase B activation exhibited overexpression of the EGF receptor. In contrast, no significant differences in MAP kinase activation could be detected between individual GBMs. Our data show that EGF receptor overexpression seems to be responsible for activation of the protein kinase B whereas PTEN deletion seems to play a minor role in the dysregulation of this important pathway in human GBM in vivo.
Schlegel
Jürgen
J
Institute of Pathology, Munich Technical University, Ismaninger Strasse 22, D-81675 Muenchen, Germany. schlegel@neuropathologie-muenchen.de
Piontek
Guido
G
Mennel
Hans-Dieter
HD
D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000201:enzymology* / Q000378:metabolism; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000201:enzymology* / Q000378:metabolism; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D005909:Glioblastoma / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis
D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D066246:ErbB Receptors; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human