Selenoprotein W modulates control of cell cycle entry

Wayne Chris Hawkes, Thomas T Y Wang, Zeynep Alkan, B. Diane Richter, Kevin Dawson

Research output: Contribution to journalArticle

32 Scopus citations

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 × 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.

Original languageEnglish (US)
Pages (from-to)229-244
Number of pages16
JournalBiological Trace Element Research
Volume131
Issue number3
DOIs
StatePublished - Dec 2009

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Keywords

  • Cancer
  • Cell cycle entry
  • Chemoprevention
  • G1/S transition
  • Nutrition
  • Selenium

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Inorganic Chemistry
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Hawkes, W. C., Wang, T. T. Y., Alkan, Z., Richter, B. D., & Dawson, K. (2009). Selenoprotein W modulates control of cell cycle entry. Biological Trace Element Research, 131(3), 229-244. https://doi.org/10.1007/s12011-009-8367-0