title: PPARγ is functionally expressed in clear cell renal cell carcinoma.
abstract: Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have been demonstrated to exert an inhibitory effect on cell growth in several tumor models, including clear cell renal cell carcinoma (CCRCC). PPARγ has therefore been proposed to be a potential therapeutic target. Thus, the PPARγ 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 PPARγ 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 PPARγ. Potential mutations were analyzed by DNA sequencing of the 6 coding exons of the PPARγ 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 PPARγ1 isoform. The expression level of PPARγ 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 PPARγ target gene, in CCRCC cell lines cultured in the presence of rosiglitazone, a PPARγ agonist. A strong induction was found in the 3 cell lines tested, indicating that PPARγ is functional in all these cell lines. In conclusion, we show here that PPARγ is expressed and functional in CCRCC, prerequisites for being a potential target for CCRCC treatment.
authors.affiliation: CNRS UMR 6061, Institut de Génétique et Développement, Université Rennes 1, 35043 Rennes, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Collet
authors.forename: Sandrine
authors.initials: S
authors.lastname: Théoleyre
authors.forename: Julie
authors.initials: J
authors.lastname: Rageul
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Mottier
authors.forename: Florence
authors.initials: F
authors.lastname: Jouan
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rioux-Leclercq
authors.forename: Patricia
authors.initials: P
authors.lastname: Fergelot
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Patard
authors.forename: Damien
authors.initials: D
authors.lastname: Masson
authors.forename: Marc G
authors.initials: MG
authors.lastname: Denis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques; D047495:PPAR gamma / Q000235:genetics* / Q000502:physiology; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D047495:PPAR gamma