| Autor: |
Carlson BA; Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Yoo MH, Tobe R, Mueller C, Naranjo-Suarez S, Hoffmann VJ, Gladyshev VN, Hatfield DL |
| Jazyk: |
angličtina |
| Zdroj: |
Carcinogenesis [Carcinogenesis] 2012 Sep; Vol. 33 (9), pp. 1806-13. Date of Electronic Publication: 2012 Jul 12. |
| DOI: |
10.1093/carcin/bgs230 |
| Abstrakt: |
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 with ~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 upregulation of another selenoenzyme, glutathione peroxidase 2 (GPx2), and components of the glutathione (GSH) system, including those that generate reduced GSH. 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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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