Nrf2-activated expression of sulfiredoxin contributes to urethane-induced lung tumorigenesis

Murli Mishra, Hong Jiang, Hedy A. Chawsheen, Matthieu Gerard, Michel B. Toledano, Qiou Wei

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Lung cancer is the leading cause of cancer death worldwide. Cigarette smoking and exposure to chemical carcinogens are among the risk factors of lung tumorigenesis. In this study, we found that cigarette smoke condensate and urethane significantly stimulated the expression of sulfiredoxin (Srx) at the transcript and protein levels in cultured normal lung epithelial cells, and such stimulation was mediated through the activation of nuclear related factor 2 (Nrf2). To study the role of Srx in lung cancer development in vivo, mice with Srx wildtype, heterozygous or knockout genotype were subjected to the same protocol of urethane treatment to induce lung tumors. By comparing tumor multiplicity and volume between groups of mice with different genotype, we found that Srx knockout mice had a significantly lower number and smaller size of lung tumors. Mechanistically, we demonstrated that loss of Srx led to a decrease of tumor cell proliferation as well as an increase of tumor cell apoptosis. These data suggest that Srx may have an oncogenic role that contributes to the development of lung cancer in smokers or urethane-exposed human subjects.

Original languageEnglish
Pages (from-to)216-226
Number of pages11
JournalCancer Letters
Volume432
DOIs
StatePublished - Sep 28 2018

Bibliographical note

Funding Information:
This work was partially supported by the National Institutes of Health (NCI grant number P30CA177558 , R01CA222596 ), Department of Defense (grant number W81XWH-16-1-0203 ), American Cancer Society (grant number RSG-16-213-01-TBE ) and Kentucky Lung Cancer Research Program 2016 .

Publisher Copyright:
© 2018 Elsevier B.V.

Keywords

  • Antioxidant
  • Cell growth and proliferation
  • Oxidative stress
  • Peroxiredoxins
  • Signal transduction

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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