Peroxisome proliferator-activated receptor gamma 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 gamma (PPARgamma) expression and assessed whether PPARgamma ligands influence carcinoma growth. EXPERIMENTAL DESIGN: We examined the presence and cellular distribution of PPARgamma protein in 42 normal endometria, 32 endometria with hyperplasia, and 103 endometria with endometrial carcinoma by immunohistochemistry. We then compared PPARgamma mRNA expression in endometrial carcinoma with that in normal endometria using real-time reverse transcription-PCR. We subsequently confirmed expression of PPARgamma mRNA by real-time reverse transcription-PCR and PPARgamma protein by immunoblotting in endometrial carcinoma cell lines (Ishikawa, Sawano, and RL95-2 cells). We further examined the effects of PPARgamma agonist 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), a naturally occurring PPARgamma 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-PGJ2. RESULTS: PPARgamma 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. PPARgamma 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 PPARgamma and p21 expression in endometrial carcinoma (P < 0.0001). There was a significant negative association between the body mass index and PPARgamma labeling index of carcinoma tissue in the patients with endometrial carcinoma (P < 0.0001). PPARgamma mRNA was expressed abundantly in normal endometria but not in endometrial carcinoma. We showed that PPARgamma agonist 15d-PGJ2 inhibited cell proliferation and induced p21 mRNA of endometrial carcinoma cell lines. CONCLUSION: We showed the expression of PPARgamma in human endometrial carcinoma and the effects of PPARgamma ligand in endometrial carcinoma cells. These findings suggest that a PPARgamma ligand, 15d-PGJ2, has antiproliferative activity against endometrial carcinoma.