PPARγ is functionally expressed in clear cell renal cell carcinoma

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.