title: Secretory phospholipase A2 mediates human esophageal adenocarcinoma cell growth and proliferation via ERK 1/2 pathway.
abstract: OBJECTIVE
  Secretory phospholipase-A2 (sPLA2) mediates growth and proliferation of human esophageal adenocarcinoma cells (HEAC). Two major molecular pathways of cancer growth regulation include extracellular signal-regulated kinase 1/2 (ERK 1/2) and protein kinase-B (AKT). Phospholipase enzymes have been demonstrated to significantly influence these two growth regulating pathways in other tumor cells. We hypothesize sPLA2 to mediate HEAC growth control through ERK 1/2 and AKT.
  
  
  METHODS
  Verified HEAC (FLO-1), treated with either the mitogen-activated protein kinase kinase selective inhibitor (PD98059) or with group IIa sPLA2-specific inhibitor, were assessed for ERK1/2 phosphorylation and AKT activation after tumor necrosis factor-alpha stimulation, as well as for viability, proliferation, and apoptosis responses.
  
  
  RESULTS
  PD98059 significantly inhibited ERK 1/2 activation, reduced cell viability, and reduced proliferation (p<0.05). sPLA2 inhibition attenuated ERK 1/2 activation (p<0.01) but had no effect on AKT activation or apoptosis.
  
  
  CONCLUSIONS
  Specific inhibition of group IIa sPLA2 directly reduces HEAC viability and proliferation by attenuating ERK 1/2 activation with no effect on AKT activation or apoptosis. This may indicate that the mechanism of action of sPLA2 is mainly the induction of growth arrest.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Miral R
authors.initials: MR
authors.lastname: Sadaria
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Yu
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Meng
authors.forename: David A
authors.initials: DA
authors.lastname: Fullerton
authors.forename: T Brett
authors.initials: TB
authors.lastname: Reece
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Weyant
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D054497:Phospholipases A2, Secretory