Peroxisome Proliferator-Activated Receptor γ and Growth Inhibition by Its Ligands in Uterine Endometrial Carcinoma

Purpose: In this study, we evaluated the correlation between endometrial carcinoma and peroxisome proliferator-activated receptor γ (PPARγ) expression and assessed whether PPARγ ligands influence carcinoma growth. Experimental Design: We examined the presence and cellular distribution of PPARγ protein in 42 normal endometria, 32 endometria with hyperplasia, and 103 endometria with endometrial carcinoma by immunohistochemistry. We then compared PPARγ mRNA expression in endometrial carcinoma with that in normal endometria using real-time reverse transcription-PCR. We subsequently confirmed expression of PPARγ mRNA by real-time reverse transcription-PCR and PPARγ protein by immunoblotting in endometrial carcinoma cell lines (Ishikawa, Sawano, and RL95-2 cells). We further examined the effects of PPARγ agonist 15-deoxy-Δ 12,14 -prostaglandin J 2 (15d-PGJ 2 ), a naturally occurring PPARγ ligand, to these endometrial carcinoma cell lines. We also examined the status of apoptosis and p21 mRNA expression of these endometrial carcinoma cell lines following addition of 15d-PGJ 2 . Results: PPARγ immunoreactivity was detected in 11 of 23 (48%) of proliferative-phase endometrium, 14 of 19 (74%) of secretory-phase endometrium, 27 of 32 (84%) of endometrial hyperplasia, and 67 of 103 (65%) of carcinoma cases. PPARγ immunoreactivity was significantly lower in endometrial carcinoma than in secretory-phase endometrium ( P = 0.012) and endometrial hyperplasia ( P = 0.006). There was a significant positive association between the status of PPARγ and p21 expression in endometrial carcinoma ( P < 0.0001). There was a significant negative association between the body mass index and PPARγ labeling index of carcinoma tissue in the patients with endometrial carcinoma ( P < 0.0001). PPARγ mRNA was expressed abundantly in normal endometria but not in endometrial carcinoma. We showed that PPARγ agonist 15d-PGJ 2 inhibited cell proliferation and induced p21 mRNA of endometrial carcinoma cell lines. Conclusion: We showed the expression of PPARγ in human endometrial carcinoma and the effects of PPARγ ligand in endometrial carcinoma cells. These findings suggest that a PPARγ ligand, 15d-PGJ 2 , has antiproliferative activity against endometrial carcinoma.