Contrasting patterns of regulation of the antioxidant selenoproteins, thioredoxin reductase, and glutathione peroxidase, in cancer cells.
There is strong evidence that selenium protects against certain human cancers, but the underlying mechanism is unknown. Glutathione peroxidase (GPX1) and thioredoxin reductase (TR), the most abundant antioxidant selenium-containing proteins in mammals, have been implicated in this protection. We analyzed the expression of TR and GPX1 in the following model cancer systems: (1) liver tumors in TGFalpha/c-myc transgenic mice; (2) human prostate cell lines from normal and cancer tissues; and (3) p53-induced apoptosis in a human colon cancer cell line. TR was induced while GPX1 was repressed in malignancies relative to controls in transgenic mice and prostate cell lines. In the colon cell line, p53 expression resulted in elevated GPX1, but repressed TR. The data indicate that TR and GPX1 are regulated in a contrasting manner in the cancer systems tested and reveal the p53-dependent regulation of selenoprotein expression. The data suggest that additional studies on selenoprotein regulation in different cancers are required to evaluate future implementation of selenium as a dietary supplement in individuals at risk for developing certain cancers.
Gladyshev
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Department of Biochemistry, University of Nebraska, Lincoln, Nebraska, 68588, USA. vng@unlinfo2.unl.edu
Factor
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Housseau
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Hatfield
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D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics; D002460:Cell Line; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D005979:Glutathione Peroxidase / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D011467:Prostate / Q000201:enzymology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology; D013880:Thioredoxin-Disulfide Reductase / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000502:physiology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016271:Proto-Oncogene Proteins c-myc; D016211:Transforming Growth Factor alpha; D016159:Tumor Suppressor Protein p53; D005979:Glutathione Peroxidase; D013880:Thioredoxin-Disulfide Reductase