Selenoprotein deficiency and high levels of selenium compounds can effectively inhibit hepatocarcinogenesis in transgenic mice

• Published in: Oncogene Vol. 24; no. 54; pp. 8003 - 8011
• Main Authors: NOVOSELOV, Sergey V, CALVISI, Diego F, LABUNSKYY, Vyacheslav M, FACTOR, Valentina M, CARLSON, Bradley A, FOMENKO, Dmitri E, MOUSTAFA, Mohamed E, HATFIELD, Dolph L, GLADYSHEV, Vadim N
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 01.12.2005; Nature Publishing Group
• Subjects: Animal models; Animals; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; c-Myc protein; Cancer; Cancer research; Carcinoma, Hepatocellular - prevention & control; Cell physiology; Cell proliferation; Cell Proliferation - drug effects; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Clinical trials; Detoxification; Diet; Disease prevention; Electrophoresis, Polyacrylamide Gel; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Genotypes; Glutathione Peroxidase - metabolism; Homeostasis; Liver cancer; Liver Neoplasms, Experimental - prevention & control; Medical research; Mice; Mice, Transgenic; Mitosis - drug effects; Molecular and cellular biology; Molecular weight; Myc protein; Selenium; Selenium compounds; Selenium Compounds - administration & dosage; Selenium Compounds - pharmacology; Selenium Radioisotopes; Selenoproteins; Selenoproteins - deficiency; Thioredoxin Reductase 1; Thioredoxin-Disulfide Reductase - metabolism; Transforming growth factor-a; Transgenic animals; Transgenic mice; Tumorigenesis; United States > US; redox regulation; cancer prevention; Deficiency; Rodentia; Malignant tumor; Carcinogenesis; Prevention; selenocysteine; Vertebrata; Regulation(control); Selenoprotein; Mammalia; Mouse; Selenium
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1208940

The micronutrient element selenium (Se) has been shown to be effective in reducing the incidence of cancer in animal models and human clinical trials. Selenoproteins and low molecular weight Se compounds were implicated in the chemopreventive effect, but specific mechanisms are not clear. We examined the role of Se and selenoproteins in liver tumor formation in TGFalpha/c-Myc transgenic mice, which are characterized by disrupted redox homeostasis and develop liver cancer by 6 months of age. In these mice, both Se deficiency and high levels of Se compounds suppressed hepatocarcinogenesis. In addition, both treatments induced expression of detoxification genes, increased apoptosis and inhibited cell proliferation. Within low-to-optimal levels of dietary Se, tumor formation correlated with expression of most selenoproteins. These data suggest that changes in selenoprotein expression may either suppress or promote tumorigenesis depending on cell type and genotype. Since dietary Se may have opposing effects on cancer, it is important to identify the subjects who will benefit from Se supplementation as well as those who will not.