title: Selective blockade of prostaglandin E2 receptors EP2 and EP4 signaling inhibits proliferation of human endometriotic epithelial cells and stromal cells through distinct cell cycle arrest.
abstract: OBJECTIVE
  To determine interactions between prostaglandin (PG) E(2) signaling and proliferation of endometriotic cells to increase our knowledge about PGE(2) signaling in the pathogenesis of endometriosis in humans.
  
  
  METHODS
  Immortalized human endometriotic epithelial and stromal cells were used as an in vitro model. Effects of inhibition of PGE(2) receptors on proliferation of endometriotic cells and associated cell cycle regulation were determined.
  
  
  METHODS
  College Veterinary Medicine and Biomedical Sciences, Texas A&M University.
  
  
  METHODS
  Not available.
  
  
  METHODS
  None.
  
  
  METHODS
  Cell proliferation, cell viability, cell cycle, regulation of cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors.
  
  
  RESULTS
  Selective blockade of EP2/EP4 inhibited proliferation of human endometriotic cells by inducing cell cycle arrest at the G(1)-S and G(2)-M checkpoints in epithelial cells and at the G(2)-M checkpoint in stromal cells. This cell cycle arrest during specific checkpoints was associated with distinct regulation of respective cyclins and cyclin-dependent kinases. Inhibition of EP1 did not decrease endometriotic cell proliferation.
  
  
  CONCLUSIONS
  For the first time data from the present study provide a direct molecular link between PGE(2) signaling and proliferation of endometriotic cells and suggest that inhibition of EP2/EP4 could be a potential nonestrogen (E) treatment option for endometriosis in women.
authors.affiliation: Reproductive Endocrinology and Cell Signaling Laboratory, Department of Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas 77843, USA.
authors.forename: JeHoon
authors.initials: J
authors.lastname: Lee
authors.forename: Sakhila K
authors.initials: SK
authors.lastname: Banu
authors.forename: Royce
authors.initials: R
authors.lastname: Rodriguez
authors.forename: Anna
authors.initials: A
authors.lastname: Starzinski-Powitz
authors.forename: Joe A
authors.initials: JA
authors.lastname: Arosh
mesh_terms: D001713:Biphenyl Compounds / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004715:Endometriosis / Q000188:drug therapy / Q000378:metabolism*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects; D005260:Female; D006801:Humans; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D018078:Receptors, Prostaglandin E / Q000187:drug effects*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015398:Signal Transduction / Q000187:drug effects*; D017154:Stromal Cells / Q000378:metabolism; D044004:Xanthones / Q000494:pharmacology
chemical_list: D001713:Biphenyl Compounds; C545644:PTGER2 protein, human; C545650:PTGER4 protein, human; D011448:Prostaglandin Antagonists; D034741:RNA, Small Interfering; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D044004:Xanthones; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; C046926:AH 23848; D018844:Cyclin-Dependent Kinases