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Prx I suppresses K-ras-driven lung tumorigenesis by opposing redox-sensitive ERK/cyclin D1 pathway.


ABSTRACT: 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-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. 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.

SUBMITTER: Park YH 

PROVIDER: S-EPMC3704122 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Prx I suppresses K-ras-driven lung tumorigenesis by opposing redox-sensitive ERK/cyclin D1 pathway.

Park Young-Ho YH   Kim Sun-Uk SU   Lee Bo-Kyoung BK   Kim Hyun-Sun HS   Song In-Sung IS   Shin Hye-Jun HJ   Han Ying-Hao YH   Chang Kyu-Tae KT   Kim Jin-Man JM   Lee Dong-Seok DS   Kim Yeul-Hong YH   Choi Chang-Min CM   Kim Bo-Yeon BY   Yu Dae-Yeul DY  

Antioxidants & redox signaling 20130613 5


<h4>Aims</h4>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.<h4>Results</h4>Using human-lung adenocarcinoma tissues and lung-sp  ...[more]

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