title: The PPARgamma antagonist T0070907 suppresses breast cancer cell proliferation and motility via both PPARgamma-dependent and -independent mechanisms.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor gamma (PPARγ) is overexpressed in many types of cancer, including breast cancer, and it is regulated by ligand binding and post-translational modifications. It was previously demonstrated that endogenous transactivation promotes an aggressive phenotype of malignant breast cells. This study examines whether selective antagonism of PPARγ with T0070907 is a potential strategy for breast cancer therapy.
  
  
  METHODS
  PPARγ activation was inhibited using both pharmacological and molecular approaches and proliferation, apoptosis, migration and invasion were measured in MDA-MB-231 and MCF-7 breast cancer cells.
  
  
  RESULTS
  T0070907 treatment inhibited proliferation, invasion and migration but did not significantly affect apoptosis. Molecular inhibition using a dominant negative (Δ462) receptor yielded similar results. T007 also mediated a dose-dependent decrease in phosphorylation of PPARγ, and its ability to bind to DNA, and may directly affect mitogen-activated protein kinase signaling.
  
  
  CONCLUSIONS
  These data indicate that inhibiting endogenous PPARγ signaling may be a promising new approach to breast cancer therapy.
authors.affiliation: University of Kentucky College of Medicine, Department of Molecular and Biomedical Pharmacology and the Markey Cancer Center, 800 Rose St., Room MS305, Lexington, KY 40536-0298, USA.
authors.forename: Yekaterina Y
authors.initials: YY
authors.lastname: Zaytseva
authors.forename: Natalie K
authors.initials: NK
authors.lastname: Wallis
authors.forename: R Chase
authors.initials: RC
authors.lastname: Southard
authors.forename: Michael W
authors.initials: MW
authors.lastname: Kilgore
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009361:Neoplasm Invasiveness; D047495:PPAR gamma / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use*; D020218:Response Elements / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D001549:Benzamides; D004273:DNA, Neoplasm; D047495:PPAR gamma; D011725:Pyridines; C458508:T 0070907; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases