In the present study, we examine whether human pancreatic carcinoma cells express peroxisome proliferator-activated receptor γ (PPARγ)and the effect of PPARγ activation by its selective ligand on cellular growth in pancreatic cancer cells. Immunohistochemical study of resected human pancreata using a polyclonal PPARγ antibody revealed that PPARγ protein expression in the nuclei of carcinoma cells was observed in 9 of 10 pancreatic adenocarcinomas. In contrast,normal pancreatic duct epithelial cells in the samples expressed no PPARγ. Reverse transcription-PCR and Northern blot analysis demonstrated that all four tested human pancreatic cancer cell lines,PK-1, PK-8, PK-9, and MIA Paca-2, expressed PPARγ mRNA. Luciferase assay in PK-1 cells showed that troglitazone, a selective ligand for PPARγ, transactivated the transcription of a peroxisome proliferator response element-driven promoter in a dose-dependent fashion. Troglitazone inhibited the growth of all four pancreatic carcinoma cell lines in a dose-dependent manner. Cell cycle analysis by flow cytometry demonstrated that troglitazone induced G₁ arrest in PK-1 cells. To examine the role of cyclin-dependent kinase inhibitors in the G₁ arrest by troglitazone, we determined p27^Kip1, p21^Cip1/Waf1, or p18^Ink4cprotein expression by Western blot analysis in troglitazone-treated PK-1 cells. Troglitazone increased p27^Kip1 but not p21^Cip1/Waf1 or p18^Ink4c protein levels in time- and dose-dependent manners. To clarify the functional importance of p27^Kip1 in the cell growth inhibition by troglitazone,we examined the effect of an antisense oligonucleotide against p27^Kip1 on the inhibition of cell proliferation by troglitazone. In PK-1 cells treated with an antisense oligonucleotide to p27^Kip1, troglitazone-induced inhibition of cell growth was not observed. In contrast, troglitazone inhibited cell proliferation in cells that had been transfected with control mismatch oligonucleotide. These results suggest that human pancreatic carcinoma cells express functional PPARγ and that PPARγ activation by troglitazone induced growth inhibition associated with G₁cell cycle arrest in pancreatic carcinoma cells. It has also been indicated that p27^Kip1 may be a key molecule in the inhibition of cell growth by troglitazone. All these results suggest that PPARγ could be considered as a possible target molecule for treatment in human pancreatic carcinomas.