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	Mohamed A Nasr, Mark J Fedele, Karyn Esser, Alan M Diamond
Journal	Free radical biology & medicine (Free Radic Biol Med) Vol. 37 Issue 2 Pg. 187-95 (Jul 15 2004) ISSN: 0891-5849 [Print] United States
PMID	15203190 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Free Radicals Intracellular Signaling Peptides and Proteins Proteins Proto-Oncogene Proteins Glutathione Peroxidase AKT1 protein, human Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt Ribosomal Protein S6 Kinases, 70-kDa Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 p38 Mitogen-Activated Protein Kinases Selenium Glutathione Peroxidase GPX1 GPX1 protein, human
Topics	Alleles Blotting, Western Cell Line, Tumor Cytoplasm (enzymology) DNA Damage Free Radicals Glutathione Peroxidase (metabolism) Humans Immunoblotting Intracellular Signaling Peptides and Proteins Loss of Heterozygosity Mitogen-Activated Protein Kinase 1 (metabolism) Mitogen-Activated Protein Kinase 3 (metabolism) Phosphorylation Protein Serine-Threonine Kinases (metabolism) Proteins (metabolism) Proto-Oncogene Proteins (metabolism) Proto-Oncogene Proteins c-akt Ribosomal Protein S6 Kinases, 70-kDa (metabolism) Selenium (pharmacology) Signal Transduction Transfection p38 Mitogen-Activated Protein Kinases (metabolism) Glutathione Peroxidase GPX1 GADD45 Proteins

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