title: Dual role of the antioxidant enzyme peroxiredoxin 6 in skin carcinogenesis.
abstract: The antioxidant enzyme peroxiredoxin 6 (Prdx6) is a key regulator of the cellular redox balance, particularly under stress conditions. We identified Prdx6 as an important player in different phases of skin carcinogenesis. Loss of Prdx6 in mice enhanced the susceptibility to skin tumorigenesis, whereas overexpression of Prdx6 in keratinocytes of transgenic mice had the opposite effect. The tumor-preventive effect of Prdx6, which was observed in a human papilloma virus 8-induced and a chemically induced tumor model, was not due to alterations in keratinocyte proliferation, apoptosis, or in the inflammatory response. Rather, endogenous and overexpressed Prdx6 reduced oxidative stress as reflected by the lower levels of oxidized phospholipids in the protumorigenic skin of Prdx6 transgenic mice and the higher levels in Prdx6-knockout mice than in control animals. In contrast to its beneficial effect in tumor prevention, overexpression of Prdx6 led to an acceleration of malignant progression of existing tumors, revealing a dual function of this enzyme in the pathogenesis of skin cancer. Finally, we found strong expression of PRDX6 in keratinocytes of normal human skin and in the tumor cells of squamous cell carcinomas, indicating a role of Prdx6 in human skin carcinogenesis. Taken together, our data point to the potential usefulness of Prdx6 activators or inhibitors for controlling different stages of skin carcinogenesis.
authors.affiliation: Department of Biology, Institute of Molecular Health Sciences, Institute of Clinical Pathology, Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Frank
authors.initials: F
authors.lastname: Rolfs
authors.forename: Marcel
authors.initials: M
authors.lastname: Huber
authors.forename: Florian
authors.initials: F
authors.lastname: Gruber
authors.forename: Friederike
authors.initials: F
authors.lastname: Böhm
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Pfister
authors.forename: Valery N
authors.initials: VN
authors.lastname: Bochkov
authors.forename: Erwin
authors.initials: E
authors.lastname: Tschachler
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.forename: Daniel
authors.initials: D
authors.lastname: Hohl
authors.forename: Matthias
authors.initials: M
authors.lastname: Schäfer
authors.forename: Sabine
authors.initials: S
authors.lastname: Werner
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000328:Adult; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D063646:Carcinogenesis / Q000378:metabolism; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D054465:Peroxiredoxin VI / Q000172:deficiency / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D015127:9,10-Dimethyl-1,2-benzanthracene; D054465:Peroxiredoxin VI