Effect of ligand activation of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) in human lung cancer cell lines.

There is compelling evidence that peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) mediates terminal differentiation and is associated with inhibition of cell growth. However, it was recently suggested that growth of two human lung cancer cell lines is enhanced by PPARbeta/delta. The goal of the present study was to provide insight in resolving this controversy. Therefore, the effect of ligand activation of PPARbeta/delta in A549 and H1838 human lung cancer cell lines was examined using two high affinity PPARbeta/delta ligands. Ligand activation of PPARbeta/delta caused up-regulation of a known PPARbeta/delta target gene, angiopoietin-like 4 (Angptl4) but did not influence expression of phosphatase and tensin homolog (PTEN) or phosphorylation of protein kinase B (Akt), and did not affect cell growth. Results from this study demonstrate that two human lung cancer cell lines respond to ligand activation of PPARbeta/delta by modulation of target gene expression (Angptl4), but fail to exhibit significant modulation of cell proliferation.