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.

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.

Related Concept Videos

The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.