title: Selenoprotein W modulates control of cell cycle entry.
abstract: The present study was conducted to identify targets of selenium (Se) provided to cultured human cells in physiologically relevant doses and forms. Breast and prostate epithelial cells were supplemented with Se provided as 100 nM sodium selenite or high-Se serum and gene expression was profiled with DNA microarrays. Pure sodium selenite affected expression of 560 genes in MCF-10A breast cells, including 60 associated with the cell cycle (p = 2.8 x 10(-16)). Selenoprotein W (SEPW1) was the only selenoprotein messenger RNA (mRNA) increased by both sodium selenite (specific) and high-Se serum (physiologic). SEPW1 small interfering RNA inhibited G1-phase progression and increased G1-phase gene transcripts, while decreasing S-phase and G2/M-phase gene transcripts, indicating the cell cycle was interrupted at the G1/S transition. SEPW1 mRNA levels were maximal during G1-phase, dropped after the G1/S transition and increased again after G2/M-phase. SEPW1-underexpressing prostate cells had increased mRNA for BCL2, which can induce a G1 arrest, and decreased mRNA for RBBP8 and KPNA2, which modulate the Rb/p53 checkpoint pathway. These results suggest that SEPW1 and the G1/S transition are physiological targets of Se in breast and prostate epithelial cells.
authors.affiliation: USDA Agricultural Research Service, Western Human Nutrition Research Center, University of California at Davis, Davis, CA, USA. wayne.hawkes@ars.usda.gov
authors.forename: Wayne Chris
authors.initials: WC
authors.lastname: Hawkes
authors.forename: Thomas T Y
authors.initials: TT
authors.lastname: Wang
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Alkan
authors.forename: B Diane
authors.initials: BD
authors.lastname: Richter
authors.forename: Kevin
authors.initials: K
authors.lastname: Dawson
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012643:Selenium / Q000378:metabolism / Q000494:pharmacology; D051151:Selenoprotein W / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D018038:Sodium Selenite / Q000494:pharmacology
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C495240:SELENOW protein, human; D051151:Selenoprotein W; D012643:Selenium; D018038:Sodium Selenite