Role of MAP kinase pathways in primitive neuroectodermal tumors

Mitogen-activated protein kinase and Phosphatidy-linositol-3 kinase/Akt-med iated signaling pathways play a major role in controlling cell proliferatio n, differentiation and cell death. Phosphorylation and dephosphorylation of their specific Thr/Tyr residues is critical in determining their activity. We determined the expression pattern and activity of MAP kinases and Akt i n Primitive Neuroectodermal Tumors (PNETs). The kinase activity of extracel lular signal-regulated kinase (ERK) was higher in both primary tumors and c ell lines, as evident from the increased phosphorylation of ERK1 and ERK2. We did not observe the activation of C-jun N-terminal kinase (JNK) or p38 M APK The expression of Raf-1, a kinase acting upstream of ERK was significan tly increased in primary tumors compared to normal brain. The PI-3 kinase-a ctivated phosphorylation of Akt was also higher in primary tumors. These re sults suggest that activation of the Raf-1/ERK module of the MAP kinase pat hway play an important role in PNETs.