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.
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.
Authors: Fumin Chang; Linda S Steelman; John G Shelton; John T Lee; Patrick M Navolanic; William L Blalock; Richard Franklin; James A McCubrey Journal: Int J Oncol Date: 2003-03 Impact factor: 5.650
Authors: R J Slebos; R E Kibbelaar; O Dalesio; A Kooistra; J Stam; C J Meijer; S S Wagenaar; R G Vanderschueren; N van Zandwijk; W J Mooi Journal: N Engl J Med Date: 1990-08-30 Impact factor: 91.245
Authors: Carola A Neumann; Daniela S Krause; Christopher V Carman; Shampa Das; Devendra P Dubey; Jennifer L Abraham; Roderick T Bronson; Yuko Fujiwara; Stuart H Orkin; Richard A Van Etten Journal: Nature Date: 2003-07-31 Impact factor: 49.962
Authors: Evan A Elko; Brian Cunniff; David J Seward; Shi Biao Chia; Reem Aboushousha; Cheryl van de Wetering; Jos van der Velden; Allison Manuel; Arti Shukla; Nicholas H Heintz; Vikas Anathy; Albert van der Vliet; Yvonne M W Janssen-Heininger Journal: Antioxid Redox Signal Date: 2019-04-05 Impact factor: 8.401