Autocrine secreted insulin-like growth factor-I stimulates MAP kinase-dependent mitogenic effects in human primitive neuroectodermal tumor/medulloblastoma

Primitive neuroectodermal tumors/medulloblastoma (PNET/MB) have similaritie s to neuroectodermal progenitor cells of the developing CNS. Since insulin- like growth factor I (IGF-I) exerts pleiotrophic effects on cells in the de veloping CNS, we evaluated the production, mitogenic effects and signaling pathways of IGF-I in PNET/MB cells and found that IGF-I is an autocrine gro wth factor in human PNET/MB cell lines tested. Stimulation of DAOY cells by IGF-I led to phosphorylation of its cognate receptor (IGF-IR) and resulted in cell proliferation. These effects of IGF-I were suppressed by IGF-IR bl ocking antibodies and by PD 98059, MAP kinase pathway inhibitor, The result s demonstrate the existence of an autocrine IGF-I/IGF-IR loop and indicate that IGF-I promotes proliferation via MAP kinase pathway.