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 similarities to neuroectodermal progenitor cells of the developing CNS. Since insulin-like growth factor I (IGF-I) exerts pleiotrophic effects on cells in the developing 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 growth 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 blocking antibodies and by PD 98059, MAP kinase pathway inhibitor. The results demonstrate the existence of an autocrine IGF-I/IGF-IR loop and indicate that IGF-I promotes proliferation via MAP kinase pathway.
Patti
R
R
Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Reddy
C D
CD
Geoerger
B
B
Grotzer
M A
MA
Raghunath
M
M
Sutton
L N
LN
Phillips
P C
PC
D002455:Cell Division / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology*; D008527:Medulloblastoma / Q000473:pathology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D005419:Flavonoids; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one