Peroxisome Proliferator-Activated Receptor γ Is Highly Expressed in Pancreatic Cancer and Is Associated With Shorter Overall Survival Times

Abstract

Purpose: Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor that has been implicated in carcinogenesis and progression of various solid tumors, including pancreatic carcinoma. We aimed to clarify the expression patterns of PPARγ in pancreatic ductal carcinomas and to correlate these to clinicopathologic variables, including patient survival. Experimental Design: Array-based expression profiling of 19 microdissected carcinomas and 14 normal ductal epithelia was conducted. Additionally, Western blots of pancreatic cancer cell lines and paraffinized tissue of 129 pancreatic carcinomas were immunostained for PPARγ. For statistical analysis, Fisher's exact test, χ2 test for trends, correlation analysis, Kaplan-Meier analysis, and Cox's regression were applied. Results: Expression profiles showed a strong overexpression of PPARγ mRNA (change fold, 6.9; P = 0.04). Immunohistochemically, PPARγ expression was seen in 71.3% of pancreatic cancer cases. PPARγ expression correlated positively to higher pT stages and higher tumor grade. Survival analysis showed a significant prognostic value for PPARγ, which was found to be independent in the clinically important subgroup of node-negative tumors. Conclusions: PPARγ is commonly up-regulated in pancreatic ductal adenocarcinoma and might be a prognostic marker in this disease. Both findings corroborate the importance of PPARγ in tumor progression of pancreatic cancer.

Thiazolidinediones inhibit hepatocarcinogenesis in hepatitis B virus-transgenic mice by peroxisome proliferator-activated receptor γ-independent regulation of nucleophosmin

“…Moreover, in human pancreatic and ovarian cancers expression profiles indicate a strong overexpression of PPARc that positively correlate with higher pT stages and higher tumor grade. 29,30 Interestingly, our experiments showed that in Tg(HBV)CreKOc mice TZD administration inhibits tumor formation with a potency significantly higher than in parental and control mice. Moreover, PPARc ectopic expression in PPARc-deficient hepatocytes reduced the antiproliferative effect of TZD (Supporting Information Fig.…”

Suppression of pancreatic carcinoma growth by activating peroxisome proliferator-activated receptor γ involves angiogenesis inhibition

“…PPARγ plays an important role in insulin sensitization and differentiation of adipocytes, monocytes and macrophages [5] . Activation of PPARγ can also induce growth inhibition in human prostate cancer cells, colon cancer cells, gastric cancer cells [10] , pancreatic cancer cells [12][13][14][15][16][17] and liposarcoma cells [18] . The expression of PPARγ and its role in human pancreatic carcinoma have not been fully elucidated.…”

“…It has been shown that PPARγ gene expression is observed in a variety of tissues, including adipose tissue and tumor tissue. Some in vitro studies have recently reported that PPARγ activation has inhibitory effects on the growth of pancreatic carcinoma cells [13][14][15] , probably due to its up-regulation of cellular apoptosis and its down-regulation of tumor invasion [16][17][18] . However, little attention has previously been paid to PPARγ action on the growth of pancreatic carcinoma in vivo, especially its regulation action on tumor angiogenesis.…”

Peroxisome proliferator-activated receptor-γ inhibits pancreatic cancer cell invasion and metastasis via regulating MMP-2 expression through PTEN

“…PPARγ and its ligands have thus become one of the main focuses of basic tumor research. Currently, the results of studies on PPARγ in pancreatic cancer have demonstrated that PPARγ is highly expressed in pancreatic tumor tissues (17) and PPARγ activation by ligands inhibits the growth and arrests the cell cycle of human pancreatic cancer cells at the G1 phase through various pathways (5,(18)(19)(20). Itami et al (20) found that overexpression of PPARγ in the pancreatic cancer cell line KMP-3 led to lipid accumulation, while treatment with TGZ increased the level of p27Kip1 and thereby arrested the cell cycle at G1 phase.…”