Thioredoxin Reductase 1 Protects Against Chemically Induced Hepatocarcinogenesis Via Control of Cellular Redox Homeostasis

Overview

Journal Carcinogenesis

Specialty Oncology

Date 2012 Jul 14

PMID 22791808

Citations 29

Authors

Bradley A Carlson

Min-Hyuk Yoo

Ryuta Tobe

Charles Mueller

Salvador Naranjo-Suarez

Victoria J Hoffmann

Vadim N Gladyshev

Dolph L Hatfield

Affiliations

Soon will be listed here.

Abstract

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.

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