Higher expression of peroxisome proliferator-activated receptor γ or its activation by agonist thiazolidinedione-rosiglitazone promotes bladder cancer cell migration and invasion

Urology. 2013 May;81(5):1109.e1-6. doi: 10.1016/j.urology.2012.12.027. Epub 2013 Mar 19.

Abstract

Objective: To investigate the role of peroxisome proliferator-activated receptor γ (PPARγ) in bladder cancer (BCa) progression.

Materials and methods: The gene copy number of PPARγ in human BCa tissue samples was analyzed by fluorescence in situ hybridization. The migration and invasive ability of human BCa cell lines with different PPARγ expression levels or treated with thiazolidinedione-rosiglitazone, a PPARγ agonist and an antidiabetic drug, were investigated.

Results: PPARγ amplification was increased dramatically in BCa tissue compared with normal urothelium (38.1% vs 4.3%, P = .0082) and in tumors with lymph node metastasis compared with those without metastasis (75.0% vs 15.4%, P = .0176). The human BCa cell line 5637 with strong PPARγ expression demonstrated a greater ability for cell migration and invasion than the UMUC-3 cell line with weak PPARγ expression. Knocking down PPARγ in BCa 5637 cells led to decreased cell migration, and activation of PPARγ with thiazolidinedione-rosiglitazone promoted their migration and invasive ability.

Conclusion: PPARγ amplification in BCa could play an important role in BCa cell migration and invasion. Alteration of PPARγ expression by PPARγ-small interfering ribonucleic acid or activation by its agonist rosiglitazone, a diabetic thiazolidinedione drug, could lead to alternation of BCa cell migration and invasion.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • In Situ Hybridization, Fluorescence
  • PPAR gamma / biosynthesis
  • PPAR gamma / genetics*
  • RNA, Neoplasm / genetics*
  • Real-Time Polymerase Chain Reaction
  • Rosiglitazone
  • Thiazolidinediones / agonists*
  • Thiazolidinediones / pharmacology
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology

Substances

  • Hypoglycemic Agents
  • PPAR gamma
  • RNA, Neoplasm
  • Thiazolidinediones
  • Rosiglitazone