title: Prx I suppresses K-ras-driven lung tumorigenesis by opposing redox-sensitive ERK/cyclin D1 pathway.
abstract: OBJECTIVE
  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-ras(G12D)-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-ras(G12D)-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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  These findings provide a better understanding of oxidative stress-mediated lung tumorigenesis.
authors.affiliation: Disease Model Research Laboratory, Aging Research Center , Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Park
authors.forename: Sun-Uk
authors.initials: SU
authors.lastname: Kim
authors.forename: Bo-Kyoung
authors.initials: BK
authors.lastname: Lee
authors.forename: Hyun-Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: In-Sung
authors.initials: IS
authors.lastname: Song
authors.forename: Hye-Jun
authors.initials: HJ
authors.lastname: Shin
authors.forename: Ying-Hao
authors.initials: YH
authors.lastname: Han
authors.forename: Kyu-Tae
authors.initials: KT
authors.lastname: Chang
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Lee
authors.forename: Yeul-Hong
authors.initials: YH
authors.lastname: Kim
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Choi
authors.forename: Bo-Yeon
authors.initials: BY
authors.lastname: Kim
authors.forename: Dae-Yeul
authors.initials: DY
authors.lastname: Yu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D011905:Genes, ras / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D051267:NF-E2-Related Factor 2; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D019938:Cyclin D1; D054464:Peroxiredoxins; D048049:Extracellular Signal-Regulated MAP Kinases