Skip to main content

Advertisement

SpringerLink
Log in

Selenoprotein W Modulates Control of Cell Cycle Entry

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

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]

References

  1. G. N. Schrauzer, D. A. White, and C. J. Schneider, Cancer mortality correlation studies--III: statistical associations with dietary selenium intakes. Bioinorg. Chem., 7:23–31. (1977).

    Google Scholar 

  2. G. N. Schrauzer and W. J. Rhead, Interpretation of the methylene blue reduction test of human plasma and the possible cancer protecting effect of selenium. Experientia, 27:1069–1071 (1971).

    Article  CAS  PubMed  Google Scholar 

  3. G. F. Combs, Jr., Current evidence and research needs to support a health claim for selenium and cancer prevention. J. Nutr., 135:343–347 (2005).

    CAS  PubMed  Google Scholar 

  4. J. Gromadzinska, E. Reszka, K. Bruzelius, W. Wasowicz, and B. Akesson, Selenium and cancer: biomarkers of selenium status and molecular action of selenium supplements. Eur. J. Nutr., 47 Suppl 2:29–50 (2008).

    Google Scholar 

  5. C. Ip, Y. Dong, and H. E. Ganther, New concepts in selenium chemoprevention. Cancer Metastasis Rev., 21:281–289 (2002).

    Article  CAS  PubMed  Google Scholar 

  6. G. N. Schrauzer, Trace elements in carcinogenesis. In: H. H. Draper (ed.), Adv. Nutr. Res., Vol. 2:pp. 219–244. New York: Plenum, (1979).

  7. L. V. Papp, J. Lu, A. Holmgren, and K. K. Khanna, From selenium to selenoproteins: synthesis, identity, and their role in human health. Antioxid. Redox Signal., 9:775–806 (2007).

    Article  CAS  PubMed  Google Scholar 

  8. J. G. Yang, K. E. Hill, and R. F. Burk, Dietary selenium intake controls rat plasma selenoprotein p concentration. J. Nutr., 119:1010–1012 (1989).

    CAS  PubMed  Google Scholar 

  9. D. Behne, A. Kyriakopoulos, H. Gessner, B. Walzog, and H. Meinhold, Type i iodothyronine deiodinase activity after high selenium intake and relations between selenium and iodine metabolism in rats. J. Nutr., 122:1542–1546 (1992).

    CAS  PubMed  Google Scholar 

  10. C. Ip, Selenium inhibition of chemical carcinogenesis. Fed. Proc., 44:2573–2578 (1985).

    CAS  PubMed  Google Scholar 

  11. V. Diwadkar-Navsariwala, G. S. Prins, S. M. Swanson, L. A. Birch, V. H. Ray, S. Hedayat, D. L. Lantvit, and A. M. Diamond, Selenoprotein deficiency accelerates prostate carcinogenesis in a transgenic model. Proc. Natl. Acad. Sci. U. S. A., 103:8179–8184 (2006).

    Google Scholar 

  12. R. Irons, B. A. Carlson, D. L. Hatfield, and C. D. Davis, Both selenoproteins and low molecular weight selenocompounds reduce colon cancer risk in mice with genetically impaired selenoprotein expression. J. Nutr., 136:1311–1317 (2006).

    CAS  PubMed  Google Scholar 

  13. D. Ratnasinghe, J. A. Tangrea, M. R. Andersen, M. J. Barrett, J. Virtamo, P. R. Taylor, and D. Albanes, Glutathione peroxidase codon 198 polymorphism variant increases lung cancer risk. Cancer Res., 60:6381–6383. (2000).

    Google Scholar 

  14. Y. Ichimura, T. Habuchi, N. Tsuchiya, L. Wang, C. Oyama, K. Sato, H. Nishiyama, O. Ogawa, and T. Kato, Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant. J. Urol., 172:728–732. (2004).

    Google Scholar 

  15. Y. J. Hu and A. M. Diamond, Role of glutathione peroxidase 1 in breast cancer: loss of heterozygosity and allelic differences in the response to selenium. Cancer Res., 63:3347–3351. (2003).

    Google Scholar 

  16. G. Ravn-Haren, A. Olsen, A. Tjonneland, L. O. Dragsted, B. A. Nexo, H. Wallin, K. Overvad, O. Raaschou-Nielsen, and U. Vogel, Associations between GPX1 Pro198Leu polymorphism, erythrocyte GPX activity, alcohol consumption and breast cancer risk in a prospective cohort study. Carcinogenesis, 14:14 (2005).

    Google Scholar 

  17. J. A. Knight, U. V. Onay, S. Wells, H. Li, E. J. Shi, I. L. Andrulis, and H. Ozcelik, Genetic variants of GPX1 and SOD2 and breast cancer risk at the Ontario site of the Breast Cancer Family Registry. Cancer Epidemiol. Biomarkers Prev., 13:146–149. (2004).

    Google Scholar 

  18. M. Udler, A. T. Maia, A. Cebrian, C. Brown, D. Greenberg, M. Shah, C. Caldas, A. Dunning, D. Easton, B. Ponder, and P. Pharoah, Common germline genetic variation in antioxidant defense genes and survival after diagnosis of breast cancer. J. Clin. Oncol., 25:3015–3023 (2007).

    Article  CAS  PubMed  Google Scholar 

  19. W. C. Hawkes and M. A. Kutnink, High-performance liquid chromatographic-fluorescence determination of traces of selenium in biological materials. Anal. Biochem., 241:206–211 (1996).

    Article  CAS  PubMed  Google Scholar 

  20. P. Pozarowski and Z. Darzynkiewicz, Analysis of cell cycle by flow cytometry. Methods Mol. Biol., 281:301-311 (2004).

    CAS  PubMed  Google Scholar 

  21. Affymetrix, Affymetrix GeneChip Expression Analysis Technical Manual, Santa Clara, CA: Affymetrix, (2004).

    Google Scholar 

  22. W. M. Liu, R. Mei, X. Di, T. B. Ryder, E. Hubbell, S. Dee, T. A. Webster, C. A. Harrington, M. H. Ho, J. Baid, and S. P. Smeekens, Analysis of high density expression microarrays with signed-rank call algorithms. Bioinformatics, 18:1593–1599 (2002).

    Article  CAS  PubMed  Google Scholar 

  23. G. Dennis, Jr., B. T. Sherman, D. A. Hosack, J. Yang, W. Gao, H. C. Lane, and R. A. Lempicki, DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol., 4:P3 (2003).

  24. S. Krull, J. Thyberg, B. Bjorkroth, H. R. Rackwitz, and V. C. Cordes, Nucleoporins as components of the nuclear pore complex core structure and Tpr as the architectural element of the nuclear basket. Mol. Biol. Cell, 15:4261–4277 (2004).

    Article  CAS  PubMed  Google Scholar 

  25. S. Shibata, Y. Matsuoka, and Y. Yoneda, Nucleocytoplasmic transport of proteins and poly(A) + RNA in reconstituted Tpr-less nuclei in living mammalian cells. Genes Cells, 7:421–434 (2002).

    Article  CAS  PubMed  Google Scholar 

  26. M. Park, M. Dean, C. S. Cooper, M. Schmidt, S. J. O'Brien, D. G. Blair, and G. F. Vande Woude, Mechanism of met oncogene activation. Cell, 45:895-904 (1986).

    CAS  Google Scholar 

  27. J. J. Champoux, DNA topoisomerases: structure, function, and mechanism. Annu. Rev. Biochem., 70:369-413 (2001).

    Article  CAS  PubMed  Google Scholar 

  28. R. A. Irizarry, B. Hobbs, F. Collin, Y. D. Beazer-Barclay, K. J. Antonellis, U. Scherf, and T. P. Speed, Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics, 4:249-264 (2003).

    Article  PubMed  Google Scholar 

  29. V. G. Tusher, R. Tibshirani, and G. Chu, Significance analysis of microarrays applied to the ionizing radiation response. Proc. Natl. Acad. Sci. U. S. A., 98:5116–5121. (2001).

  30. Z. Bar-Joseph, Z. Siegfried, M. Brandeis, B. Brors, Y. Lu, R. Eils, B. D. Dynlacht, and I. Simon, Genome-wide transcriptional analysis of the human cell cycle identifies genes differentially regulated in normal and cancer cells. Proc. Natl. Acad. Sci. U. S. A., 105:955–960 (2008).

    Google Scholar 

  31. W. C. Hawkes, E. C. Wilhelmsen, and A. L. Tappel, Abundance and tissue distribution of selenocysteine-containing proteins in the rat. J. Inorg. Biochem., 23:77–92 (1985).

    Article  CAS  PubMed  Google Scholar 

  32. E. L. Patterson, R. Milstrey, and E. L. R. Stokstad, Effect of selenium in preventing exudative diathesis in chicks. Proc. Soc. Exp. Biol. Med., 95:617 (1957).

    Google Scholar 

  33. K. Schwarz and C. M. Foltz, Selenium as an integral part of Factor 3 against dietary necrotic liver degeneration. J. Am. Chem. Soc., 79:3292 (1957).

    Google Scholar 

  34. U. F. Neumann and K. Bronsch, Studies on the optimum selenium supplementation of nongravid and gravid sows. J. Vet. Med. Ser. A, 35:673–682 (1988).

    CAS  Google Scholar 

  35. B. E. R. Sandstrom, J. Carlsson, and S. L. Marklund, Variations among cultured cells in glutathione peroxidase activity in response to selenite supplementation. Biochim. Biophys. Acta, 929:148–153 (1987).

    Article  CAS  PubMed  Google Scholar 

  36. M. H. Lewin, J. R. Arthur, R. A. Riemersma, F. Nicol, S. W. Walker, E. M. Millar, A. F. Howie, and G. J. Beckett, Selenium supplementation acting through the induction of thioredoxin reductase and glutathione peroxidase protects the human endothelial cell line EAhy926 from damage by lipid hydroperoxides. Biochim. Biophys. Acta, 1593:85–92. (2002).

    Google Scholar 

  37. A. A. Sneddon, H. C. Wu, A. Farquharson, I. Grant, J. R. Arthur, D. Rotondo, S. N. Choe, and K. W. Wahle, Regulation of selenoprotein GPx4 expression and activity in human endothelial cells by fatty acids, cytokines and antioxidants. Atherosclerosis, 171:57–65 (2003).

    Article  CAS  PubMed  Google Scholar 

  38. W. Zhong and T. D. Oberley, Redox-mediated effects of selenium on apoptosis and cell cycle in the LNCaP human prostate cancer cell line. Cancer Res., 61:7071–7078 (2001).

    CAS  PubMed  Google Scholar 

  39. B. D. Arenholt, M. Abdulla, A. Jepsen, and E. J. Pedersen, Effect of organic and inorganic selenium on human keratinocytes. Trace Elem. Med., 5:29–34 (1988).

    Google Scholar 

  40. M. R. Kafai and V. Ganji, Sex, age, geographical location, smoking, and alcohol consumption influence serum selenium concentrations in the USA: Third National Health and Nutrition Examination Survey, 1988–1994. J. Trace Elem. Med. Biol., 17:13–18 (2003).

    Article  PubMed  Google Scholar 

  41. P. D. Whanger, Metabolism of selenium in humans. J. Trace Elem. Exp. Med., 11:227–240 (1998).

    Google Scholar 

  42. M. Styblo, J. Kalouskova, and J. Klas, Comparison of the kinetics of a trace and a sublethal dose of selenite in rats, with particular attention being given to blood selenium distribution. J. Trace Elem. Electrolytes Health Dis., 5:155–164 (1991).

    CAS  PubMed  Google Scholar 

  43. P. D. Whanger, Selenoprotein W: a review. Cell. Mol. Life Sci., 57:1846–1852 (2000).

    Article  CAS  PubMed  Google Scholar 

  44. H. Zeng, Selenite and selenomethionine promote HL-60 cell cycle progression. J. Nutr., 132:674–679 (2002).

    CAS  PubMed  Google Scholar 

  45. A. J. Baumgarten, J. Felthaus, and R. Wasch, Strong inducible knockdown of APC/CCdc20 does not cause mitotic arrest in human somatic cells. Cell Cycle, 8:643–646 (2009).

    CAS  PubMed  Google Scholar 

  46. P. D. Whanger, N. D. Pedersen, and P. H. Weswig, Selenium proteins in ovine tissues. II. Spectral properties of a 10,000 molecular weight selenium protein. Biochem. Biophys. Res. Commun., 53:1031–1035 (1973).

    Google Scholar 

  47. J. Bellingham, K. Gregory-Evans, M. F. Fox, and C. Y. Gregory-Evans, Gene structure and tissue expression of human selenoprotein W, SEPW1, and identification of a retroprocessed pseudogene, SEPW1P. Biochim. Biophys. Acta, 1627:140–146 (2003).

    CAS  PubMed  Google Scholar 

  48. Y. Zhang and V. N. Gladyshev, Trends in selenium utilization in marine microbial world revealed through the analysis of the global ocean sampling (GOS) project. PLOS Genet., 4:e1000095 (2008).

    Google Scholar 

  49. M. A. Albright, OSU researcher banks on mutant mice. Corvallis Gazette-Times Online. Corvallis, Oregon, (2004).

    Google Scholar 

  50. Y. Dong, H. E. Ganther, C. Stewart, and C. Ip, Identification of molecular targets associated with selenium-induced growth inhibition in human breast cells using cDNA microarrays. Cancer Res., 62:708–714. (2002).

    Google Scholar 

  51. H. Zhang, Y. Dong, H. Zhao, J. Brooks, L. Hawthorn, N. Nowak, J. Marshall, A. Gao, and C. Ip, Microarray Data Mining for Potential Selenium Targets in Chemoprevention of Prostate Cancer. Cancer Genomics & Proteomics 2:97–114 (2005).

    CAS  Google Scholar 

  52. K. El-Bayoumy and R. Sinha, Molecular chemoprevention by selenium: A genomic approach. Mutat. Res., 591:224–236 (2005).

    CAS  PubMed  Google Scholar 

  53. T. M. Cao, F. Y. Hua, C. M. Xu, B. S. Han, H. Dong, L. Zuo, X. Wang, Y. Yang, H. Z. Pan, and Z. N. Zhang, Distinct effects of different concentrations of sodium selenite on apoptosis, cell cycle, and gene expression profile in acute promyeloytic leukemia-derived NB4 cells. Ann. Hematol., 85:434–442 (2006).

    Article  CAS  PubMed  Google Scholar 

  54. H. P. Wang, F. Q. Schafer, P. C. Goswami, L. W. Oberley, and G. R. Buettner, Phospholipid hydroperoxide glutathione peroxidase induces a delay in G1 of the cell cycle. Free Radic. Res., 37:621–630 (2003).

    Article  CAS  PubMed  Google Scholar 

  55. T. J. Preston, W. J. Muller, and G. Singh, Scavenging of extracellular H2O2 by catalase inhibits the proliferation of HER-2/Neu-transformed rat-1 fibroblasts through the induction of a stress response. J. Biol. Chem., 276:9558–9564 (2001).

    Article  CAS  PubMed  Google Scholar 

  56. Y. Zhang, W. Zhao, H. J. Zhang, F. E. Domann, and L. W. Oberley, Overexpression of copper zinc superoxide dismutase suppresses human glioma cell growth. Cancer Res., 62:1205–1212 (2002).

    CAS  PubMed  Google Scholar 

  57. A. Dikiy, S. V. Novoselov, D. E. Fomenko, A. Sengupta, B. A. Carlson, R. L. Cerny, K. Ginalski, N. V. Grishin, D. L. Hatfield, and V. N. Gladyshev, SelT, SelW, SelH, and Rdx12: genomics and molecular insights into the functions of selenoproteins of a novel thioredoxin-like family. Biochemistry, 46:6871–6882 (2007).

    Article  CAS  PubMed  Google Scholar 

  58. H. Hermeking and A. Benzinger, 14-3-3 proteins in cell cycle regulation. Semin. Cancer Biol., 16:183–192 (2006).

    Article  CAS  PubMed  Google Scholar 

  59. P. A. Savitsky and T. Finkel, Redox regulation of Cdc25C. J. Biol. Chem., 277:20535–20540 (2002).

    Article  CAS  PubMed  Google Scholar 

  60. X. Wang and W. Dai, BRCA2 in mitotic exit: a new role in regulating genomic stability. Future Oncol., 2:43–46 (2006).

    Article  CAS  PubMed  Google Scholar 

  61. H. Ueda, K. Kuroda, and G. Endo, The inhibitory effect of selenium on induction of tetraploidy by dimethylarsinic acid in Chinese hamster cells. Anticancer Res., 17:1939–1943 (1997).

    CAS  PubMed  Google Scholar 

  62. S. Volik, B. J. Raphael, G. Huang, M. R. Stratton, G. Bignel, J. Murnane, J. H. Brebner, K. Bajsarowicz, P. L. Paris, Q. Tao, D. Kowbel, A. Lapuk, D. A. Shagin, I. A. Shagina, J. W. Gray, J. F. Cheng, P. J. de Jong, P. Pevzner, and C. Collins, Decoding the fine-scale structure of a breast cancer genome and transcriptome. Genome Res., 16:394–404 (2006).

    Article  CAS  PubMed  Google Scholar 

  63. R. J. Shamberger, F. F. Baughman, S. L. Kalchert, C. S. Willis, and G. C. Hoffman, Carcinogen-induced chromosomal breakage decreased by antioxidants. Proc. Natl. Acad. Sci. U. S. A., 70:1461–1463 (1973).

    Google Scholar 

  64. A. Mukherjee, A. Sharma, and G. Talukder, Effect of selenium on cadmium-induced chromosomal aberrations in bone marrow cells of mice. Toxicol. Lett., 41:23–30 (1988).

    Article  CAS  PubMed  Google Scholar 

  65. J. K. Lin and S. F. Tseng, Chromosomal aberrations and sister-chromatid exchanges induced by n nitroso-2-acetylaminofluorene and their modifications by arsenite and selenite in chinese hamster ovary cells. Mutat. Res., 265:203–210 (1992).

    CAS  PubMed  Google Scholar 

  66. E. Kowalska, S. A. Narod, T. Huzarski, S. Zajaczek, J. Huzarska, B. Gorski, and J. Lubinski, Increased rates of chromosome breakage in BRCA1 carriers are normalized by oral selenium supplementation. Cancer Epidemiol. Biomarkers Prev., 14:1302–1306. (2005).

    Google Scholar 

  67. M. Kanehisa, M. Araki, S. Goto, M. Hattori, M. Hirakawa, M. Itoh, T. Katayama, S. Kawashima, S. Okuda, T. Tokimatsu, and Y. Yamanishi, KEGG for linking genomes to life and the environment. Nucleic Acids Res., 36:D480–484 (2008).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

US Department of Agriculture CRIS project no. 5306-51530-009-00D and no. 1235-52530-003-00 and NCMHD grant no. 1 P60 MD00222 supported this research. The UC Davis Cancer Center Gene Expression Resource supported by NCI Cancer Center Support Grant P30 CA93373 performed the microarray labeling, hybridizations, and scanning. Mention of trade name, proprietary product, or specific equipment does not constitute a guarantee or warranty by the US Department of Agriculture nor does it imply approval to the exclusion of other products that may be suitable. The opinions expressed herein represent those of the authors and do not necessarily represent those of the US Department of Agriculture.

Conflict of interest

The authors have no financial or other conflicting interest in any product or service mentioned in this article.

Author information

Authors and Affiliations

  1. USDA Agricultural Research Service, Western Human Nutrition Research Center, University of California at Davis, Davis, CA, USA

    Wayne Chris Hawkes, Zeynep Alkan & B. Diane Richter

  2. USDA Agricultural Research Service, Beltsville Human Nutrition Research Center, Beltsville, MD, USA

    Thomas T. Y. Wang

  3. NCMHD Center for Excellence in Nutritional Genomics, University of California at Davis, Davis, CA, USA

    Kevin Dawson

Authors
  1. Wayne Chris Hawkes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas T. Y. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zeynep Alkan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B. Diane Richter
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kevin Dawson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wayne Chris Hawkes.

Electronic supplementary material

Below is the link to the electronic supplementary material.

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

Supplemental Table S2. Affymetrix DNA microarray probe sets affected by all three species of SEPW1 siRNA in RWPE-1 cells. (XLS 154 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hawkes, W.C., Wang, T.T.Y., Alkan, Z. et al. Selenoprotein W Modulates Control of Cell Cycle Entry. Biol Trace Elem Res 131, 229–244 (2009). https://doi.org/10.1007/s12011-009-8367-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-009-8367-0

Keywords

Search

Navigation