Effect of PPARα Ligand on TNFα -Dependent Expression of EGF Receptor in Human Glioma Cell Line

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In glioma cells, tumor necrosis factor alpha (TNFα) 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 (PPARα) have been reported to inhibit proliferation of various tumor cells. In this study, we evaluated the influence of synthetic PPARα ligand, Wy 14643, on basal and TNFα-dependent expression of EGFR in U251MG cells derived from a human malignant glioma. Northern blot analysis revealed that TNFα increased EGFR mRNA levels and that this increase was markedly suppressed by Wy 14643. However, it had only marginal effect on the basal levels of EGFR mRNA. These results demonstrate that the activation of PPARα leads to the inhibition of the TNFα-dependent EGFR expression in human malignant glioma cells.

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