Peroxisome proliferator-activated receptor γ reduces the growth rate of pancreatic cancer cells through the reduction of cyclin D1

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) forms a heterodimeric DNA-binding complex with the retinoid X receptor (RXR) and regulates the transcription of its target genes. Activation of PPARγ has been shown to induce G1 arrest and to inhibit cell growth of human pancreatic carcinoma cell lines. The purpose of the present study was to examine the effect of ligand activation of PPARγ and RXR on cell growth and on the expression of G1 cyclins in a pancreatic cancer cell line PANC-1, which expresses PPARγ at high levels. Troglitazone, a specific ligand for PPARγ, was found to cause a reduction in the growth rate and induced G1 cell cycle arrest and this effect was additive with that of 9-cis retinoic acid (9-cis RA), a ligand for RXR. Of the G1 cyclins tested, troglitazone specifically reduced the expression of cyclin D1 mRNA and the corresponding protein and this effect was also additive with 9-cis RA. These results suggest that the activation of PPARγ together with RXR may be useful for the suppression of pancreatic cancer cell growth through the reduction in cyclin D1 levels.