The non-genomic crosstalk between PPAR-gamma ligands and ERK1/2 in cancer cell lines.

Peroxisome proliferator activated receptors (PPARs) are members of the nuclear receptor superfamily acting as transcription factors. PPAR-gamma, one of the three PPAR subtypes, is expressed in many malignant and non-malignant cells and tissues. PPAR-gamma ligands influence cancer biology via both genomic as well as non-genomic events. The non-genomic action of PPAR-gamma ligands, including the activation of MAPK signaling pathways, is under intense investigation. In the presence of PPAR-gamma ligands, a rapid phosphorylation of ERK1/2 is observed in many cancer cell lines. Activated ERK1/2 elicits rapid, non-genomic cellular effects and can directly repress PPAR-gamma transcriptional activity by phosphorylation. This paper reviews the interrelation of PPAR-gamma ligands and activated ERK1/2, in relation to their antineoplastic actions in cancer cell lines, which may offer the potential for improved anticancer therapies.