Expression of peroxisome proliferator-activated receptor gamma in renal cell carcinoma and growth inhibition by its agonists

Biochem Biophys Res Commun. 2001 Sep 28;287(3):727-32. doi: 10.1006/bbrc.2001.5640.

Abstract

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. It plays a role in both adipocyte differentiation and tumorgenesis. Up-date, the up-regulation of PPAR-gamma expression is a frequent occurrence in a variety of different malignant tumors. In this study, we investigated the expression of PPAR-gamma in human renal cell carcinoma (RCC) tissues, and the role of PPAR-gamma in cell growth in human RCC-derived cell lines. Immunohistochemistry showed a strong immunoreactive expression of PPAR-gamma in all slides from cancer specimens. RT-PCR and Western blot analysis showed 3 RCC cell lines expressed PPAR-gamma mRNA and its protein. MTT assay in 3 RCC cells showed that the synthetic PPAR-gamma agonists thiazolidinedione compounds (pioglitazone and troglitazone) and the endogeneous PPAR-gamma ligand, 15-deoxy-Delta12,14-prostaglandin J(2) (15dPGJ(2)) inhibited the growth of the RCC cells. These results suggest that PPAR-gamma may become a new target in the treatment of RCC.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Blotting, Western
  • Carcinoma, Renal Cell / metabolism*
  • Cell Division
  • Chromans / pharmacology
  • Coloring Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Immunohistochemistry
  • Immunologic Factors / pharmacology
  • Kidney Neoplasms / metabolism*
  • Ligands
  • Pioglitazone
  • Prostaglandin D2 / analogs & derivatives
  • Prostaglandin D2 / pharmacology
  • RNA, Messenger / metabolism
  • Receptors, Cytoplasmic and Nuclear / biosynthesis*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tetrazolium Salts / pharmacology
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Transcription Factors / biosynthesis*
  • Transcription Factors / metabolism*
  • Troglitazone
  • Tumor Cells, Cultured
  • Up-Regulation

Substances

  • 15-deoxy-delta(12,14)-prostaglandin J2
  • Antineoplastic Agents
  • Chromans
  • Coloring Agents
  • Hypoglycemic Agents
  • Immunologic Factors
  • Ligands
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Tetrazolium Salts
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • 2,4-thiazolidinedione
  • thiazolyl blue
  • Troglitazone
  • Prostaglandin D2
  • Pioglitazone