title: Activation of PPARgamma leads to inhibition of anchorage-independent growth of human colorectal cancer cells.
abstract: OBJECTIVE
  Peroxisomal proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone receptor that provides a direct link between fatty acid metabolism and control of gene transcription. The objective of this study was to determine the biological effect(s) of PPARgamma activation in colorectal carcinoma cells.
  
  
  METHODS
  PPARgamma expression and activity were measured in 4 human colon cancer cell lines using reverse-transcription polymerase chain reaction, immunoprecipitation and immunoblotting, and transient reporter gene assays. The effects of activated PPARgamma in these cell lines were assessed in cellular proliferation and anchorage-independent growth assays. Flow cytometry was used to determine the effects of PPARgamma activation on progression through the cell cycle.
  
  
  RESULTS
  PPARgamma was expressed in all 4 colon cancer cell lines examined and was transcriptionally functional in 3 of the 4. Treatment of these cells with a selective PPARgamma activator (BRL 49653) resulted in inhibition of anchorage-independent growth. The degree of growth inhibition correlated with the level of functional PPARgamma present. Finally, activation of PPARgamma resulted in G1 cell cycle arrest.
  
  
  CONCLUSIONS
  Activation of the PPARgamma pathway in colon cancer cells has potent antiproliferative effects, suggesting that this nuclear hormone receptor may provide a novel target for prevention and treatment of colorectal cancer in humans.
authors.affiliation: Gastroenterology Division, Departments of Medicine and Cell Biology, Vanderbilt University Medical Center and Veterans Affairs Medical Center, Nashville, Tennessee, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Brockman
authors.forename: R A
authors.initials: RA
authors.lastname: Gupta
authors.forename: R N
authors.initials: RN
authors.lastname: Dubois
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000502:physiology*; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone