| First Author | Park YH | Year | 2013 |
| Journal | Antioxid Redox Signal | Volume | 19 |
| Issue | 5 | Pages | 482-96 |
| PubMed ID | 23186333 | Mgi Jnum | J:294846 |
| Mgi Id | MGI:6458853 | Doi | 10.1089/ars.2011.4421 |
| Citation | Park YH, et al. (2013) Prx I suppresses K-ras-driven lung tumorigenesis by opposing redox-sensitive ERK/cyclin D1 pathway. Antioxid Redox Signal 19(5):482-96 |
| abstractText | 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. |
