title: Pathway sensitivity analysis for detecting pro-proliferation activities of oncogenes and tumor suppressors of epidermal growth factor receptor-extracellular signal-regulated protein kinase pathway at altered protein levels.
abstract: BACKGROUND
  Mathematic models and sensitivity analyses of biologic pathways have been used for exploring the dynamics and for detecting the key components of signaling pathways.
  
  
  METHODS
  The authors previously developed a mathematic model of the epidermal growth factor receptor-extracellular signal-regulated protein kinase (EGFR-ERK) pathway using ordinary differential equations from existing EGFR-ERK pathway models. By using prolonged ERK activation as an indicator that may lead to cell proliferation under certain circumstances, in the current study, a pathway sensitivity analysis was performed to test its capability of detecting pro-proliferative activities through altered protein levels to examine the effects on ERK activation.
  
  
  RESULTS
  The analysis revealed that 12 of 20 oncoproteins and 4 of 5 tumor suppressors were detected, consistent with reported experimental works. Because pathway dynamics depend on many factors, some of which were not included in the current models, failure to detect all known oncogenes and tumor suppressors can be because of the failure to include relevant crosstalk to other pathway components.
  
  
  CONCLUSIONS
  Overall, the current results indicated that pathway sensitivity analysis is a useful approach for detecting and distinguishing pro-proliferation activities of oncoproteins and suppressed proliferative activities of tumor suppressors at altered protein levels at least in the EGFR-ERK model.
authors: Bioinformatics and Drug Design Group, Department of Pharmacy, National University of Singapore, Singapore.
authors: Hu
authors: H
authors: Li
authors: Choong Yong
authors: CY
authors: Ung
authors: Xiao Hua
authors: XH
authors: Ma
authors: Xiang Hui
authors: XH
authors: Liu
authors: Bao Wen
authors: BW
authors: Li
authors: Boon Chuan
authors: BC
authors: Low
authors: Yu Zong
authors: YZ
authors: Chen
mesh_terms: D049109:Cell Proliferation; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006801:Humans; D008962:Models, Theoretical; D009369:Neoplasms / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D015513:Oncogene Proteins; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases