title: The mitogen-activated/extracellular signal-regulated kinase kinase 1/2 inhibitor U0126 induces glial fibrillary acidic protein expression and reduces the proliferation and migration of C6 glioma cells.
abstract: The extracellular signal-regulated kinase (ERK) signaling pathway has been implicated in diverse cellular functions. ERK and its activating kinase, mitogen-activated/extracellular signal-regulated kinase kinase (MEK), are downstream of cell surface receptors known to be up-regulated in many malignant gliomas. We sought to investigate the role of ERK in glioma cell migration, proliferation and differentiation using the rat-derived C6 glioma cell line and the MEK inhibitor, U0126. Treatment of C6 cells with U0126 caused a significant concentration-dependent reduction in cell proliferation and migration and also induced expression of glial fibrillary acidic protein, a marker of astrocytic differentiation. These results suggest that the ERK pathway regulates glioma cell proliferation, migration and differentiation.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: C R P
authors.initials: CR
authors.lastname: Lind
authors.forename: C W
authors.initials: CW
authors.lastname: Gray
authors.forename: A G
authors.initials: AG
authors.lastname: Pearson
authors.forename: R E
authors.initials: RE
authors.lastname: Cameron
authors.forename: S J
authors.initials: SJ
authors.lastname: O'Carroll
authors.forename: P J
authors.initials: PJ
authors.lastname: Narayan
authors.forename: J
authors.initials: J
authors.lastname: Lim
authors.forename: M
authors.initials: M
authors.lastname: Dragunow
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001973:Bromodeoxyuridine / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism*; D005910:Glioma; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D009570:Nitriles / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D009570:Nitriles; D013778:Tetrazolium Salts; D013844:Thiazoles; C113580:U 0126; D053148:Caspase 3; C022616:thiazolyl blue; D001973:Bromodeoxyuridine