IGF receptor function and regulation in autocrine human neuroblastoma cell growth.
Insulin-like growth factor-II (IGF-II) and its receptors (type I and II IGF receptors) are expressed in the nervous system in a tissue and developmentally specific manner. We have previously shown that SH-SY5Y human neuroblastoma cells synthesize and secrete high levels of IGF-II, and respond to it with increased neuritic outgrowth, DNA synthesis, and cell proliferation. SH-SY5Y cells also produce type I IGF and IGF-II/M6P receptors; however, it is not known whether these receptors mediate the observed growth promoting effects of IGF-II. In this study, we assayed the role of type I IGF receptor and IGF-II/M6P receptor expression in mediating autocrine IGF-II induced growth. Using anti-receptor antibodies, we found that IGF-II stimulates cell proliferation via the type I IGF receptor but not via the IGF-II/M6P receptor. By Northern analysis, we detected increased mRNA expression of both receptors, with more dramatic changes in type I IGF receptor expression. Collectively, our results indicate a role for the type I IGF receptor in mediating IGF-II induced autocrine neuroblastoma cell growth.
Martin
D M
DM
Department of Neurology, University of Michigan, Ann Arbor.
Singleton
J R
JR
Meghani
M A
MA
Feldman
E L
EL
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001769:Blood; D002417:Cattle; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D016895:Culture Media, Serum-Free; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D016501:Neurites / Q000502:physiology; D009447:Neuroblastoma; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D017527:Receptor, IGF Type 2 / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000502:physiology
D000906:Antibodies; D016895:Culture Media, Serum-Free; D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1