Elevated basal reactive oxygen species and phospho-Akt in murine keratinocytes resistant to ultraviolet B-induced apoptosis

Brent D. Butts, Kevin A. Kwei, G. Tim Bowden, Margaret M Briehl

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18 Scopus citations


Resistance to apoptosis may be a critical phenotype that cells must acquire during skin carcinogenesis. The Akt kinase is a known upstream regulator of apoptosis in many cell types and has been shown to be activated by increased reactive oxygen species (ROS). We have previously demonstrated that two malignant variants (6M90 and 6R90) of the mouse keratinocyte 308 cell line have elevated ROS because of loss of catalase activity, and that this elevated ROS confers a growth advantage. We report here that in addition to a growth advantage, chronically increased ROS in the variants resulted in an increase in resistance to ultraviolet (UV) B-induced apoptosis. This resistance was due to basal increases of Akt phosphorylation in the malignant variants compared to the 308 cells. Modulation of ROS in 6M90 and 6R90 cells by catalase overexpression or antioxidant treatment resulted in decreased levels of Akt phosphorylation and subsequent loss of resistance to UVB-induced apoptosis. Conversely, treatment of 308 cells with hydrogen peroxide caused increases in Akt phosphorylation and increased apoptosis resistance. These results indicate that the chronically elevated ROS often observed in tumors may contribute to a malignant phenotype by keeping Akt in a phosphorylated state, resulting in increased apoptosis resistance.

Original languageEnglish (US)
Pages (from-to)149-157
Number of pages9
JournalMolecular Carcinogenesis
Issue number3
Publication statusPublished - Jul 1 2003



  • Cell survival
  • Oxidative stress
  • Signal pathway
  • Skin cancer

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

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