Expression of peroxisome proliferator-activated receptor γ and the growth inhibitory effect of its synthetic ligands in human salivary gland cancer cell lines

Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. It is expressed in several tissue types, including adipose tissue in which it stimulates adipogenesis. Recent studies have demonstrated that PPARγ ligands induce cellular differentiation and inhibit cell growth in carcinomas of various organs including the breast, prostate, lung, colon, stomach, bladder, and pancreas. However, whether PPARγ is expressed in human salivary gland tumors and its function in this tissue is unknown. In the present study, we examined PPARγ gene expression in human salivary gland cancer cells and tested its ligands for any antitumor effect. PPARγ mRNA was detected by RT-PCR in both benign and malignant salivary gland tumor tissues. The effect of PPARγ on cell growth was investigated using four human salivary gland cancer cell lines; HSG, AZA3, HSY and TYS, which were confirmed to express PPARγ1 mRNA and protein. Retinoid X receptor α protein, which forms heterodimers with PPARγ, was also detected in all the cells tested. Data obtained by luciferase assay indicated that the intrinsic PPARγ protein was activated by the synthetic ligands, troglitazone and pioglitazone, but not by the natural ligand, 15-deoxy-Δ12, 14-prostaglandin J2. The synthetic PPARγ ligands, particularly troglitazone, caused significant dose-dependent inhibition of cancer cell growth. Furthermore, the overexpression of PPARγ1 or PPARγ2 in cancer cells also reduced significantly their growth rate. These results suggest that PPARγ and its synthetic ligands suppress the growth of human salivary gland cancer cells and it may be a useful molecular target for cancer treatment.