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Updated: Jun 5, 2026

The Use of Reverse Phase Protein Arrays (RPPA) to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
PPARγ is functionally expressed in clear cell renal cell carcinoma
Nicolas Collet1, Sandrine Théoleyre, Julie Rageul
1CNRS UMR 6061, Institut de Génétique et Développement, Université Rennes 1, 35043 Rennes, France.
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.
Insights
Peroxisome proliferator-activated receptor gamma (PPARγ) is expressed and functional in clear cell renal cell carcinoma (CCRCC), indicating its potential as a therapeutic target for this cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Peroxisome proliferator-activated receptor gamma (PPARγ) agonists inhibit cancer cell growth, including in clear cell renal cell carcinoma (CCRCC).
- PPARγ is a potential therapeutic target for CCRCC, necessitating its expression and integrity in cancer cells.
Purpose of the Study:
- To investigate the expression, alterations, and functionality of the PPARγ gene in CCRCC specimens.
- To determine if PPARγ is a viable therapeutic target for CCRCC treatment.
Main Methods:
- Multiplex ligation-dependent probe amplification (MLPA) to detect PPARγ gene deletions.
- DNA sequencing to identify mutations in PPARγ coding exons.
- Real-time quantitative PCR to measure PPARγ transcript levels.
- Analysis of angiopoietin-like 4 expression to assess PPARγ functionality.
Main Results:
- The majority of CCRCC tumors (76.2%) showed no PPARγ alterations. Two samples (3.2%) had deletions in non-coding exon A1, and nine (14.3%) had heterozygous deletions in chromosome 3p including PPARγ.
- No mutations were found in coding exons 1-5; a silent polymorphism was detected in exon 6 (22.2%).
- PPARγ1 isoform was expressed, and reduced transcript levels correlated with higher Fuhrman grade. PPARγ was functional in CCRCC cell lines, as evidenced by angiopoietin-like 4 induction.
Conclusions:
- PPARγ is expressed and functional in clear cell renal cell carcinoma.
- The gene integrity is largely maintained, with specific deletions observed in a subset of tumors.
- PPARγ represents a promising therapeutic target for CCRCC treatment.
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