Document Detail

Cellular and molecular consequences of peroxisome proliferator-activated receptor-gamma activation in ovarian cancer cells.
MedLine Citation:
PMID:  17032502     Owner:  NLM     Status:  MEDLINE    
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated transcription factor. In addition to its canonical role in lipid and glucose metabolism, PPAR-gamma controls cell proliferation, death, and differentiation in several tissues. Here we have examined the expression of PPAR-gamma in ovarian tumors and the cellular and molecular consequences of its activation in ovarian cancer cells. PPAR-gamma was expressed in a large number of epithelial ovarian tumors and cell lines. The PPAR-gamma ligand ciglitazone inhibited the growth and clonogenic survival of ovarian cancer cells, inducing cell cycle arrest and cell death. Growth inhibition by ciglitazone was reversed by the PPAR-gamma antagonist GW9662, indicating the involvement of PPAR-gamma-dependent mechanisms. Microarray-based gene profiling revealed complex changes in the transcriptional program of ovarian cancer cells on treatment with ciglitazone and identified multiple pathways that may contribute to PPAR-gamma ligands' antitumor activity. Genes upregulated by ciglitazone were predominantly associated with metabolic, differentiation, and tumor-suppressor pathways, whereas downregulated genes were involved in cell proliferation, cell cycle, cell organization, and steroid biosynthesis. Collectively, our data indicate that PPAR-gamma activation by selective agonists is a valid strategy for ovarian cancer therapy and prevention, and should be tested alone and in combination with other anticancer drugs.
Sara Vignati; Veronica Albertini; Andrea Rinaldi; Ivo Kwee; Cristina Riva; Rita Oldrini; Carlo Capella; Francesco Bertoni; Giuseppina M Carbone; Carlo V Catapano
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neoplasia (New York, N.Y.)     Volume:  8     ISSN:  1476-5586     ISO Abbreviation:  Neoplasia     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-10-11     Completed Date:  2006-12-01     Revised Date:  2013-03-13    
Medline Journal Info:
Nlm Unique ID:  100886622     Medline TA:  Neoplasia     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  851-61     Citation Subset:  IM    
Laboratory of Experimental Oncology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
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MeSH Terms
Cell Cycle
Cell Survival
Gene Expression Profiling
Ovarian Neoplasms / genetics,  metabolism*
PPAR gamma / metabolism*
Thiazolidinediones / pharmacology
Transcription, Genetic
Tumor Cells, Cultured
Reg. No./Substance:
0/Ligands; 0/PPAR gamma; 0/Thiazolidinediones; 74772-77-3/ciglitazone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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