title: Peroxisome-proliferator-activated receptors γ and β/δ mediate vascular endothelial growth factor production in colorectal tumor cells.
abstract: BACKGROUND
  Peroxisome-proliferator-activated receptors (PPARs) are nuclear receptors for fatty acids and their derivatives. PPAR subtypes PPARγ and PPARβ/δ are suspected to modulate cancer development in the colon, but their exact role is still discussed controversially.
  
  
  METHODS
  The present study investigated the impact of PPARγ and PPARβ/δ on vascular endothelial growth factor (VEGF) and cyclooxygenase 2 (COX-2) expressions induced by synthetic and physiological agonists in the colorectal tumor cell lines SW480 and HT29 using reporter gene assays, qRT-PCR and ELISA.
  
  
  RESULTS
  Activation of both PPARγ and PPARβ/δ induced expression of VEGF mRNA and protein in a PPAR-dependent way. The PPARγ agonists ciglitazone and PGJ(2) were the most effective inducers with up to ninefold and threefold increases in VEGF mRNA in SW480 and HT29 cultures, respectively. VEGF secretion was doubled in both cell lines. The PPARβ/δ agonists GW501516 and PGI(2) caused stimulations of only 1.5-fold in both cell lines. In addition, all PPAR agonists induced COX-2 mRNA and secretion of the COX-2 product PGE(2) in HT29 cells. However, this effect was not blocked by knock-down of PPAR expression nor was it essential for VEGF expression as shown by the lack of effect of the COX-2 inhibitor SC236.
  
  
  CONCLUSIONS
  In summary, our results identify both PPARγ and PPARβ/δ as an alternative COX-independent mechanism of VEGF induction in colorectal tumor cells.
authors.affiliation: Department of Medicine 1, Clinic for Internal Medicine I, Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria.
authors.forename: Clemens
authors.initials: C
authors.lastname: Röhrl
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kaindl
authors.forename: Inga
authors.initials: I
authors.lastname: Koneczny
authors.forename: Xenia
authors.initials: X
authors.lastname: Hudec
authors.forename: David M
authors.initials: DM
authors.lastname: Baron
authors.forename: Jürgen S
authors.initials: JS
authors.lastname: König
authors.forename: Brigitte
authors.initials: B
authors.lastname: Marian
mesh_terms: D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics; D006801:Humans; D047494:PPAR delta / Q000819:agonists / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D048068:PPAR-beta / Q000819:agonists / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C425931:GW 501516; D047494:PPAR delta; D047495:PPAR gamma; D048068:PPAR-beta; D047492:Peroxisome Proliferator-Activated Receptors; D012333:RNA, Messenger; D013844:Thiazoles; D045162:Thiazolidinediones; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; C039671:ciglitazone