Thioredoxin reductase 1 protects against chemically induced hepatocarcinogenesis via control of cellular redox homeostasis

被引：49

作者：

Carlson, Bradley A. ^{[1
]}

Yoo, Min-Hyuk ^{[1
]}

Tobe, Ryuta ^{[1
]}

Mueller, Charles ^{[1
]}

Naranjo-Suarez, Salvador ^{[1
]}

Hoffmann, Victoria J. ^{[2
]}

Gladyshev, Vadim N. ^{[3
,4
]}

Hatfield, Dolph L. ^{[1
]}

机构：

[1] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Bethesda, MD 20892 USA

[2] NIH, Off Director, Diagnost & Res Serv Branch, Bethesda, MD 20892 USA

[3] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Boston, MA 02115 USA

来源：

CARCINOGENESIS | 2012年 / 33卷 / 09期

基金：

美国国家卫生研究院;

关键词：

CANCER-THERAPY; GLUTATHIONE; SELENOPROTEINS; DEFICIENCY; SELENIUM; CELLS; GENE; THIOREDOXIN-REDUCTASE-1; SELENOCYSTEINE; EMBRYOGENESIS;

D O I：

10.1093/carcin/bgs230

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1806 / 1813

页数：8

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