Details

Autor(en) / Beteiligte

• Wu, Lisha
• Jiang, Hong
• Chawsheen, Hedy A
• Mishra, Murli
• Young, Matthew R
• Gerard, Matthieu
• Toledano, Michel B
• Colburn, Nancy H
• Wei, Qiou

Titel

Tumor promoter-induced sulfiredoxin is required for mouse skin tumorigenesis

Ist Teil von

• Carcinogenesis (New York), 2014-05, Vol.35 (5), p.1177-1184

Ort / Verlag

UK: Oxford University Press

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Summary Srx induced by tumor promoter reduces hyperoxidized Prxs, increases cells’ ability to survive through oxidative stress by inhibition of TPA-induced apoptosis and facilitates skin tumor development. Sulfiredoxin (Srx), the exclusive enzyme that reduces the hyperoxidized inactive form of peroxiredoxins (Prxs), has been found highly expressed in several types of human skin cancer. To determine whether Srx contributed to skin tumorigenesis in vivo, Srx null mice were generated on an FVB background. Mouse skin tumorigenesis was induced by a 7,12-dimethylbenz[α]anthracene/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA) protocol. We found that the number, volume and size of papillomas in Srx−/− mice were significantly fewer compared with either wild-type (Wt) or heterozygous (Het) siblings. Histopathological analysis revealed more apoptotic cells in tumors from Srx−/− mice. Mechanistic studies in cell culture revealed that Srx was stimulated by TPA in a redox-independent manner. This effect was mediated transcriptionally through the activation of mitogen-activated protein kinase and Jun-N-terminal kinase. We also demonstrated that Srx was capable of reducing hyperoxidized Prxs to facilitate cell survival under oxidative stress conditions. These findings suggested that loss of Srx protected mice, at least partially, from DMBA/TPA-induced skin tumorigenesis. Therefore, Srx has an oncogenic role in skin tumorigenesis and targeting Srx may provide novel strategies for skin cancer prevention or treatment.