Prx I Suppresses K-ras-Driven Lung Tumorigenesis by Opposing Redox-Sensitive ERK/Cyclin D1 Pathway
- Authors
- Park, Young-Ho; Kim, Sun-Uk; Lee, Bo-Kyoung; Kim, Hyun-Sun; Song, In-Sung; Shin, Hye-Jun; Han, Ying-Hao; Chang, Kyu-Tae; Kim, Jin-Man; Lee, Dong-Seok; Kim, Yeul-Hong; Choi, Chang-Min; Kim, Bo-Yeon; Yu, Dae-Yeul
- Issue Date
- 8월-2013
- Publisher
- MARY ANN LIEBERT, INC
- Citation
- ANTIOXIDANTS & REDOX SIGNALING, v.19, no.5, pp.482 - 496
- Indexed
- SCIE
SCOPUS
- Journal Title
- ANTIOXIDANTS & REDOX SIGNALING
- Volume
- 19
- Number
- 5
- Start Page
- 482
- End Page
- 496
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/102596
- DOI
- 10.1089/ars.2011.4421
- ISSN
- 1523-0864
- 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.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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