Effect of PPAR alpha ligand on TNF alpha-dependent expression of EGF receptor in human glioma cell line

Abstract

In glioma cells, tumor necrosis factor alpha (TNFalpha) was reported to increase the number of epidermal growth factor receptor (EGFR) that mediates EGF-dependent cell proliferation. On the other hand, ligands for peroxisome proliferator-activated receptor alpha (PPARalpha) have been reported to inhibit proliferation of various tumor cells. In this study, evaluated was the influence of synthetic PPARalpha ligand, Wy14643, on basal and TNFalpha-dependent expression of EGFR in U251MG cells derived from a human malignant glioma. Northern blot analysis revealed that TNFalpha increased EGFR mRNA levels and that this increase was markedly suppressed by Wy14643. However, it had only marginal effect on the basal levels of EGFR mRNA. These results demonstrate that the activation of PPARalpha leads to the inhibition of the TNFalpha-dependent EGFR expression in human malignant glioma cells.