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 pathway s in human glioblastoma cells and found a constitutive phosphorylation of e ither Akt or mitogen-activated protein kinase (MAPK) under serum free condi tions. In all but one cell line Wortmannin-sensitive activation of Akt coul d be attributed to the loss of functional PTEN protein. All cell lines with Akt activation exhibited only weak phosphorylation of the MAPK signal path way, whereas those without constitutive Akt activation demonstrated high le vels of phosphorylated MAPK under serum free conditions. Our data might ind icate the presence of two functional subtypes of glioblastoma multiforme, s ince Akt and MAPK are involved in cellular survival and proliferation signa lling, respectively. (C) 2000 Elsevier Science Ireland Ltd. All rights rese rved.