title: PC12h-R cell, a subclone of PC12 cells, shows EGF-induced neuronal differentiation and sustained signaling.
abstract: Unlike nerve growth factor (NGF), epidermal growth factor (EGF) does not induce neuronal differentiation but promotes proliferation of the rat pheochromocytoma PC12 cells. We found that PC12h-R, a subclone of PC12 cells, differentiated into neuron-like cells in response to EGF as well as to NGF. PC12h-R cells treated with EGF extended neurites, attenuated cell proliferation, and increased the levels of tyrosine hydroxylase protein synthesis and of acetylcholinesterase activity as those treated with NGF. The EGF-induced differentiation of PC12h-R cells was not mediated by the indirect activation of p140trkA by EGF. In addition, EGF induced the sustained tyrosine phosphorylation of the EGF receptor, mitogen-activated protein (MAP) kinases, and 46 and 52 kDa proteins, and the prolonged activation of MAP kinases in PC12h-R cells compared with the parent PC12h, which does not show EGF-induced differentiation. The response of PC12h-R cells to EGF was not simply due to an increase in the level of EGF receptor protein. These results indicated that the duration of EGF-induced signaling might determine the cellular response of PC12 cells between cell proliferation and neuronal differentiation.
authors.affiliation: Division of Protein Biosynthesis, Institute for Protein Research, Osaka University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: T
authors.initials: T
authors.lastname: Ikeuchi
authors.forename: S
authors.initials: S
authors.lastname: Aimoto
authors.forename: H
authors.initials: H
authors.lastname: Hatanaka
mesh_terms: D000310:Adrenal Gland Neoplasms; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D002999:Clone Cells; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D007700:Kinetics; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D016716:PC12 Cells; D010673:Pheochromocytoma; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D009414:Nerve Growth Factors; D010750:Phosphoproteins; D019000:Phosphotyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D017871:Calcium-Calmodulin-Dependent Protein Kinases