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

C R P Lind; C W Gray; A G Pearson; R E Cameron; S J O'Carroll; P J Narayan; J Lim; M Dragunow

doi:10.1016/j.neuroscience.2006.05.038

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

Neuroscience. 2006 Sep 15;141(4):1925-33. doi: 10.1016/j.neuroscience.2006.05.038. Epub 2006 Jun 30.

Authors

C R P Lind¹, C W Gray, A G Pearson, R E Cameron, S J O'Carroll, P J Narayan, J Lim, M Dragunow

Affiliation

¹ Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand.

PMID: 16809005
DOI: 10.1016/j.neuroscience.2006.05.038

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Analysis of Variance
Animals
Blotting, Western / methods
Bromodeoxyuridine / metabolism
Butadienes / pharmacology*
Caspase 3 / metabolism
Cell Count / methods
Cell Line, Tumor
Cell Movement / drug effects*
Cell Proliferation / drug effects*
Cell Survival / drug effects
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology*
Gene Expression / drug effects*
Glial Fibrillary Acidic Protein / genetics
Glial Fibrillary Acidic Protein / metabolism*
Glioma
Immunohistochemistry / methods
Mice
Nitriles / pharmacology*
Tetrazolium Salts
Thiazoles

Substances

Butadienes
Enzyme Inhibitors
Glial Fibrillary Acidic Protein
Nitriles
Tetrazolium Salts
Thiazoles
U 0126
Caspase 3
thiazolyl blue
Bromodeoxyuridine