title: The mechanism of COX-2 regulating HERG channel in gastric cancer cells.
abstract: OBJECTIVE
  To elucidate the signal transduction pathway, by which cyclooxygenase-2 (COX-2) regulates human erg-related gene (HERG) current in gastric cancer cells.
  
  
  METHODS
  The HERG mRNA, protein and current in gastric cancer cells transfected with or without COX-2 antisense vector were measured by RT-PCR, Western blot and patch-clamp, respectively. Cyclic adenosine monophosphate (cAMP) concentration in gastric cancer cells transfected with or without COX-2 antisense vector was measured by ELISA.
  
  
  RESULTS
  Transfection with COX-2 antisense vector did not alter the expression of HERG mRNA and protein, but it diminished the amplitude of HERG current in gastric cancer cells (p < 0.05). The cAMP concentration in gastric cancer cells transfected with COX-2 antisense vector was lower than that in parental gastric cancer cells (p < 0.05). COX-2 inhibitor and PGE2 had influence on the HERG current in gastric cancer cells. COX-2 inhibitor reduced the amplitude of HERG current in gastric cancer cells and PGE2 enhanced the amplitude. However, in gastric cancer cells transfected with HERG mutant deleting cAMP-binding domain, both COX-2 inhibitor and PGE2 did not show significant effects on HERG current. cAMP agonist enhanced the amplitude of HERG current and cAMP antagonist reduced the amplitude in gastric cancer cells. Both agonist and antagonist of cAMP had no significant effect on HERG current in gastric cancer cells transfected with HERG mutant deleting cAMP binding domain. PKA inhibitor did not influence the HERG current whether in parental gastric cancer cells or in gastric cancer cells transfected with HERG mutant.
authors.forename: X D
authors.initials: XD
authors.lastname: Shao
authors.forename: X Z
authors.initials: XZ
authors.lastname: Guo
authors.forename: L N
authors.initials: LN
authors.lastname: Ren
authors.forename: H
authors.initials: H
authors.lastname: Lin
mesh_terms: D000068579:Celecoxib; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000502:physiology*; D006801:Humans; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D015232:Dinoprostone