Abstract
Selenium (Se) in supraphysiological concentrations is a potent chemopreventive in many cancer models, but the mechanisms and their physiological relevance to dietary cancer prevention are not clear. We grew tumorigenic (MCF-7) and non-tumorigenic (MCF-10A) human mammary epithelial cells in media containing low-Se calf serum (11 nM Se), ± 100 nM sodium selenite. The experiment was performed three times, using freshly seeded cultures each time. Messenger RNA expression profiles were measured with Affymetrix HG-U133 Plus 2.0 microarrays. Glutathione peroxidase 3 and selenophosphate synthetase 2 were over-expressed in tumor cells 5-fold and 2.5-fold, respectively, whereas glutathione peroxidase 1, selenoprotein P and selenoprotein M were under-expressed 512-, 80- and 8-fold, respectively. SEPW1 mRNA was increased 2- to 3-fold by Se in both cell lines, and was the only selenoprotein RNA affected by added Se. In MCF-10A cells, Se disproportionately affected expression of nuclear genes, genes coding for transcription factors, and genes associated with protein phosphorylation, cell cycle and mitosis. USDA Projects 5306-51530-009-00D and 1235-52530-003-00 and NCMHD Grant 1 P60 MD00222 and NCI Grant P30 CA93373 supported this research.
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