Thioredoxin reductase 1 protects against chemically induced hepatocarcinogenesis via control of cellular redox homeostasis
Menée sur un modèle murin, cette étude montre qu'une séléno-enzyme, la thiorédoxine réductase de type 1, protège contre l'hépatocarcinogenèse chimiquement induite en contrôlant l'homéostasie redox des cellules
Thioredoxin reductase 1 (TR1) controls the redox state of protein thiols in mammalian cells and has been shown to have roles in both preventing and promoting cancer. To define the role of this selenoenzyme in hepatocellular carcinoma development, we examined tumor incidence in the liver of mice with tissue-specific knockout of mouse TR1 subjected to the liver carcinogen, diethylnitrosamine (DEN). TR1-deficient livers manifested ~90% tumor incidence compared to ~16% in control livers. The TR1-dependent effect was observed independent of sex, and, in control mice, tumorigenesis did not affect the expression of TR1. On the other hand, we observed up-regulation of another selenoenzyme, glutathione peroxidase 2, and components of the glutathione system, including those that generate reduced glutathione. Overall, this study shows that TR1 protects against chemically induced hepatocarcinogenesis via the control of the cellular redox state, whereas its role in promoting this type of cancer is minimal.
http://carcin.oxfordjournals.org/content/early/2012/07/12/carcin.bgs230.abstract