Ppar Gamma Is Functionally Expressed In Clear Cell Renal Cell Carcinoma

Peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists have been demonstrated to exert an inhibitory effect on cell growth in several tumor models, including clear cell renal cell carcinoma (CCRCC). PPAR gamma has therefore been proposed to be a potential therapeutic target. Thus, the PPAR gamma gene must be expressed and not altered in cancer cells. We have therefore analyzed tumor specimens collected from 63 patients with CCRCC who underwent partial or total nephrectomy. The multiplex ligation-dependent probe amplification (MLPA) assay was used to detect deletions in the PPAR gamma gene. The majority of the tumors (48/63; 76.2%) did not present alterations. Two samples (3.2%) presented a deletion of the non-coding exon A1. Nine samples (14.3%) showed large heterozygous deletions in chromosome 3p including PPAR gamma. Potential mutations were analyzed by DNA sequencing of the 6 coding exons of the PPAR gamma gene, No mutation was found in exons 1-5. In exon 6, a silent polymorphism was detected in 14 samples (22.2%). CCRCC were found to express the PPAR gamma 1 isoform. The expression level of PPAR gamma was measured by real-time quantitative PCR. A significantly reduced transcript level was associated with an elevated Fuhrman grade. Finally, we analyzed the expression of angiopoietin-like 4, a known PPAR gamma target gene, in CCRCC cell lines cultured in the presence of rosiglitazone, a PPAR gamma agonist. A strong induction was found in the 3 cell lines tested, indicating that PPAR gamma is functional in all these cell lines. In conclusion, we show here that PPAR gamma is expressed and functional in CCRCC, prerequisites for being a potential target for CCRCC treatment.