title: Peroxisome proliferator-activated receptor gamma regulates E-cadherin expression and inhibits growth and invasion of prostate cancer.
abstract: Peroxisome proliferator-activated receptor gamma (PPARgamma) might not be permissive to ligand activation in prostate cancer cells. Association of PPARgamma with repressing factors or posttranslational modifications in PPARgamma protein could explain the lack of effect of PPARgamma ligands in a recent randomized clinical trial. Using cells and prostate cancer xenograft mouse models, we demonstrate in this study that a combination treatment using the PPARgamma agonist pioglitazone and the histone deacetylase inhibitor valproic acid is more efficient at inhibiting prostate tumor growth than each individual therapy. We show that the combination treatment impairs the bone-invasive potential of prostate cancer cells in mice. In addition, we demonstrate that expression of E-cadherin, a protein involved in the control of cell migration and invasion, is highly up-regulated in the presence of valproic acid and pioglitazone. We show that E-cadherin expression responds only to the combination treatment and not to single PPARgamma agonists, defining a new class of PPARgamma target genes. These results open up new therapeutic perspectives in the treatment of prostate cancer.
authors.affiliation: Equipe Avenir, INSERM U540, 60 rue de Navacelles, F-34090 Montpellier, France.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Annicotte
authors.forename: Irena
authors.initials: I
authors.lastname: Iankova
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Miard
authors.forename: Vanessa
authors.initials: V
authors.lastname: Fritz
authors.forename: David
authors.initials: D
authors.lastname: Sarruf
authors.forename: Anna
authors.initials: A
authors.lastname: Abella
authors.forename: Marie-Laurence
authors.initials: ML
authors.lastname: Berthe
authors.forename: Danièle
authors.initials: D
authors.lastname: Noël
authors.forename: Arnaud
authors.initials: A
authors.lastname: Pillon
authors.forename: François
authors.initials: F
authors.lastname: Iborra
authors.forename: Pierre
authors.initials: P
authors.lastname: Dubus
authors.forename: Thierry
authors.initials: T
authors.lastname: Maudelonde
authors.forename: Stéphane
authors.initials: S
authors.lastname: Culine
authors.forename: Lluis
authors.initials: L
authors.lastname: Fajas
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D009361:Neoplasm Invasiveness / Q000473:pathology; D009368:Neoplasm Transplantation; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D000077205:Pioglitazone; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D016160:Retinoblastoma Protein / Q000378:metabolism; D045162:Thiazolidinediones / Q000627:therapeutic use; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D015820:Cadherins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D047495:PPAR gamma; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D045162:Thiazolidinediones; D014635:Valproic Acid; D006655:Histone Deacetylases; D000077205:Pioglitazone