Prx i suppresses K-ras-driven lung tumorigenesis by opposing redox-sensitive ERK/Cyclin D1 pathway

Young Ho Park, Sun Uk Kim, Bo Kyoung Lee, Hyun Sun Kim, In Sung Song, Hye Jun Shin, Ying Hao Han, Kyu Tae Chang, Jin Man Kim, Dong Seok Lee, Yeul Hong Kim, Chang Min Choi, Bo Yeon Kim, Dae Yeul Yu

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)


Aims: Coupled responses of mutated K-ras and oxidative stress are often an important etiological factor in non-small-cell lung cancer (NSCLC). However, relatively few studies have examined the control mechanism of oxidative stress in oncogenic K-ras-driven NSCLC progression. Here, we studied whether the redox signaling pathway governed by peroxiredoxin I (Prx I) is involved in K-ras G12D-mediated lung adenocarcinogenesis. Results: Using human-lung adenocarcinoma tissues and lung-specific K-rasG12D-transgenic mice, we found that Prx I was significantly up-regulated in the tumor regions via activation of nuclear erythroid 2-related factor 2 (Nrf2) transcription. Interestingly, the increased reactive oxygen species (ROS) by null mutation of Prx I greatly promoted K-rasG12D-driven lung tumorigenesis in number and size, which appeared to require the activation of the ROS-dependent extracellular signal-regulated kinase (ERK)/cyclin D1 pathway. Innovation: Taken together, these results suggest that Prx I functions as an Nrf2-dependently inducible tumor suppressant in K-ras-driven lung adenocarcinogenesis by opposing ROS/ERK/cyclin D1 pathway activation. Conclusion: These findings provide a better understanding of oxidative stress-mediated lung tumorigenesis. Antioxid. Redox Signal. 19, 482-496.

Original languageEnglish
Pages (from-to)482-496
Number of pages15
JournalAntioxidants and Redox Signaling
Issue number5
Publication statusPublished - 2013 Aug 10

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cell Biology


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