title: GPx-1 modulates Akt and P70S6K phosphorylation and Gadd45 levels in MCF-7 cells.
abstract: Selenium has been shown to prevent cancer in animal models, and recent data indicate it is likely to be effective in humans as well. One selenium-containing protein, the cytoplasmic form of glutathione peroxidase (GPx-1), has been implicated in cancer risk and development by genetic studies identifying at-risk alleles and loss of heterozygosity in tumors. In order to evaluate the biological consequences of GPx-1 overexpression, human MCF-7 cells were stably transfected with a GPx-1 expression construct and the effects of GPx-1 on protein kinases associated with stress responses were determined. GPx-1 overexpression affected phosphorylation of p70S6K, whereas Erk1/2 and p38 MAPK were not affected. Site-specific phosphorylation of Akt declined and the levels of Gadd45, a DNA damage response protein, increased significantly as a consequence of elevated GPx-1 expression. Effects on p70S6K and Gadd45 after selenium supplementation have been reported, and given previous data demonstrating a role for GPx-1 in cancer etiology, these results support the concept that the chemopreventive properties of selenium may be due, at least in part, to its role in regulating GPx-1.
authors.affiliation: Department of Human Nutrition, University of Illinois at Chicago, 60612, USA.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Nasr
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Fedele
authors.forename: Karyn
authors.initials: K
authors.lastname: Esser
authors.forename: Alan M
authors.initials: AM
authors.lastname: Diamond
mesh_terms: D000483:Alleles; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000201:enzymology; D004249:DNA Damage; D005609:Free Radicals; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D019656:Loss of Heterozygosity; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D012643:Selenium / Q000494:pharmacology; D015398:Signal Transduction; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1; D000097642:GADD45 Proteins
chemical_list: D005609:Free Radicals; D005979:Glutathione Peroxidase; D047908:Intracellular Signaling Peptides and Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D012643:Selenium; D048051:p38 Mitogen-Activated Protein Kinases; D000094765:Glutathione Peroxidase GPX1; D000097642:GADD45 Proteins; C494918:AKT1 protein, human; C000722067:GPX1 protein, human