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

Hu Li, Yong Ung Choong, Hua Ma Xiao, Hui Liu Xiang, Wen Li Bao, Chuan Low Boon, Zong Chen Yu

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4246-4263
Number of pages18
JournalCancer
Volume115
Issue number18
DOIs
StatePublished - Sep 15 2009

Keywords

  • Biologic networks
  • Epidermal growth factor receptor-extracellular signal-regulated protein kinase pathway
  • Oncogene
  • Pathway simulation
  • System biology

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this