Selenoprotein W Modulates Control of Cell Cycle Entry

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

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.

Keywords

Selenium Cancer G1/S transition Cell cycle entry Nutrition Chemoprevention 

Abbreviations

Se

selenium

SEPW1

selenoprotein W

GPX

glutathione peroxidase

FBS

fetal bovine serum

SAM

significance analysis of microarrays

GO

gene ontology

RT-PCR

reverse transcriptase-polymerase chain reaction

PBS

phosphate-buffered saline

RBBP8

retinoblastoma binding protein 8

KPNA2

karyopherin alpha 2 (RAG cohort 1, importin alpha 1)

BCL2

B cell CLL/lymphoma 2

TPR

translocated promoter region [to activated MET oncogene]

MET

met proto-oncogene [hepatocyte growth factor receptor]

Supplementary material

12011_2009_8367_MOESM1_ESM.xls (125 kb)
Supplemental Table S1. Affymetrix DNA microarray probe sets affected by 100 nM selenite in MCF-10A cells. (XLS 125 kb)
12011_2009_8367_MOESM2_ESM.xls (154 kb)
Supplemental Table S2. Affymetrix DNA microarray probe sets affected by all three species of SEPW1 siRNA in RWPE-1 cells. (XLS 154 kb)

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Copyright information

© US Government 2009

Authors and Affiliations

  • Wayne Chris Hawkes
    • 1
  • Thomas T. Y. Wang
    • 2
  • Zeynep Alkan
    • 1
  • B. Diane Richter
    • 1
  • Kevin Dawson
    • 3
  1. 1.USDA Agricultural Research Service, Western Human Nutrition Research CenterUniversity of California at DavisDavisUSA
  2. 2.USDA Agricultural Research ServiceBeltsville Human Nutrition Research CenterBeltsvilleUSA
  3. 3.NCMHD Center for Excellence in Nutritional GenomicsUniversity of California at DavisDavisUSA

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