Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Carcinogenesis. 2012 Sep;33(9):1806-13. doi: 10.1093/carcin/bgs230. Epub 2012 Jul 12.
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.
硫氧还蛋白还原酶 1（TR1）控制哺乳动物细胞中蛋白质巯基的氧化还原状态，并且已经显示在预防和促进癌症方面都具有作用。为了确定这种硒酶在肝细胞癌发展中的作用，我们研究了经肝致癌物二乙基亚硝胺（DEN）处理后组织特异性敲除小鼠 TR1 的小鼠肝脏中的肿瘤发生率。与对照组肝脏相比，TR1 缺陷肝脏的肿瘤发生率约为 90％，而对照组肝脏的肿瘤发生率约为 16％。TR1 依赖性作用与性别无关，并且在对照小鼠中，肿瘤发生不会影响 TR1 的表达。另一方面，我们观察到另一种硒酶谷胱甘肽过氧化物酶 2（GPx2）以及谷胱甘肽（GSH）系统的组成部分，包括产生还原型 GSH 的成分的上调。总体而言，这项研究表明，TR1 通过控制细胞氧化还原状态来防止化学诱导的肝癌发生，而其在促进这种类型的癌症中的作用则微不足道。
