title: The human Ec peptide: the active core of a progression growth factor with species-specific mode of action.
abstract: OBJECTIVE
  Preferential IGF-1Ec expression has been firmly associated with skeletal muscle repair mechanisms, post-infarction remodeling of the myocardium, the pathophysiology of endometriosis and prostate cancer biology. Therefore, we have studied the possible biological significance of synthetic Ec peptide, a putative cleavage product of IGF-1Ec in PC-3 cells and C2C12 myoblasts.
  
  
  METHODS
  We had previously designed and synthesized commercially peptides corresponding to the human Ec and its mouse igf1 counterpart as well as synthetic peptides that correspond to parts of the hEc. Using proliferation and mitogenic signaling assays, we tested their effect on PC-3 cells and C2C12 myoblasts at different doses and in different culture conditions.
  
  
  RESULTS
  Human Ec, hEc, was documented as exerting progression but not competence growth factor actions, activating ERK1/2 without affecting Akt phosphorylation in PC-3 cells. A narrow concentration range of hEc (5-50nM) stimulated the growth of PC-3 cells grown in culture media supplemented with 10% FBS. hEc did not stimulate the growth of PC-3 cells cultured with media containing 0.5% FBS or in mouse C2C12 myoblasts under any culture conditions. The activity of hEc was blocked by a neutralizing anti-human IGF-1Ec antibody but not by a neutralizing anti-human IGF-1 receptor antibody. The synthetic mouse Ec was inactive in human PC-3 cells; however, it stimulated significantly the proliferation of mouse C2C12. By analyzing the bioactivity of synthetic hEc fragments, we documented that hEc's active core is located in the last 4aa of its C-terminal end.
  
  
  CONCLUSIONS
  The hEc peptide is an important progression factor for human PC-3 prostate cancer cells.
authors.affiliation: Department of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Goudi-Athens, Greece.
authors.forename: Efstathia
authors.initials: E
authors.lastname: Papageorgiou
authors.affiliation: Department of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Goudi-Athens, Greece.
authors.forename: Anastassios
authors.initials: A
authors.lastname: Philippou
authors.affiliation: Department of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Goudi-Athens, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Armakolas
authors.affiliation: Department of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Goudi-Athens, Greece.
authors.forename: Panagiotis F
authors.initials: PF
authors.lastname: Christopoulos
authors.affiliation: Department of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Goudi-Athens, Greece.
authors.forename: Andreas
authors.initials: A
authors.lastname: Dimakakos
authors.affiliation: Department of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Goudi-Athens, Greece. mkoutsil@med.uoa.gr.
authors.forename: Michael
authors.initials: M
authors.lastname: Koutsilieris
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D032448:Myoblasts, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D000072417:Protein Domains; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013045:Species Specificity; D013997:Time Factors
chemical_list: C583557:IGF1 protein, human; D010446:Peptide Fragments; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases