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Toxicology and Environmental Health Sciences

, Volume 2, Issue 1, pp 25–38 | Cite as

Identification of novel 17\-estradiol (E2) target genes using cross-experiment gene expression datasets

  • Won Cheol Yim
  • Changwon Keum
  • Saehwan Kim
  • Yeojeong Cho
  • Byung-Moo Lee
  • Yongeun Kwon
Original Paper

Abstract

17β-estradiol (E2) is an environmental estrogen-like chemicals that is known to affect mainly reproductive functions of exposed targets. Although microarray based toxicogenomics approach allows the investigation of the potential risks of E2 in DNA level, the underling mechanisms related to their toxic effect is not fully understood. In this work, we identified genes responding toE2 by analyzing cross-experiment public gene expression datasets that studied on E2 using RankProd algorithm. We have identified 348 DEGs which play important roles in fatty acid metabolism, infection, and DNA repair. This result was also compared with conventional PubMed data mining analysis.

Keywords

17β-estradiol E2 Cross-experiment Rank-Prod Algorithm Risk assessment DNA microarray Cross-experiment in-silico analysis 

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References

  1. 1.
    Carlsen, E., Giwercman, A., Keiding, N. & Skakkebaek, N. E. Evidence for decreasing quality of semen during past 50 years.BMJ (Clinical Research Ed.)305, 609–613 (1992).PubMedCrossRefGoogle Scholar
  2. 2.
    Sharpe, R. M. Declining sperm counts in men-is there an endocrine cause?The Journal of Endocrinology 136, 357–360 (1993).PubMedCrossRefGoogle Scholar
  3. 3.
    Sharpe, R. M. & Skakkebaek, N. E. Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract?Lancet. 341, 1392–1395 (1993).PubMedCrossRefGoogle Scholar
  4. 4.
    O’Donnell, L., Robertson, K. M., Jones, M. E. & Simpson, E. R. Estrogen and Spermatogenesis.Endocr. Rev. 22, 289–318 (2001).PubMedCrossRefGoogle Scholar
  5. 5.
    McMurray, R. W. Sex hormones in the pathogenesis of systemic lupus erythematosus.Frontiers in Bioscience: A Journal and Virtual Library 6, E193–206 (2001).CrossRefGoogle Scholar
  6. 6.
    Greene, G. L.et al. Sequence and expression of human estrogen receptor complementary DNA.Science 231, 1150–1154 (1986).PubMedCrossRefGoogle Scholar
  7. 7.
    Kuiper, G. G., Enmark, E., Pelto-Huikko, M., Nilsson, S. & Gustafsson, J. A. Cloning of a novel receptor expressed in rat prostate and ovary.Proceedings of the National Academy of Sciences of the United States of America 93, 5925–5930 (1996).PubMedCrossRefGoogle Scholar
  8. 8.
    Kuiper, G. G. J. M.et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors α and β.Endocrinology 138, 863–870 (1997).PubMedCrossRefGoogle Scholar
  9. 9.
    Mosselman, S., Polman, J. & Dijkema, R. ER beta: identification and characterization of a novel human estrogen receptor.FEBS Letters 392, 49–53 (1996).PubMedCrossRefGoogle Scholar
  10. 10.
    Marino, M., Pallottini, V. & Trentalance, A. Estrogens cause rapid activation of IP3-PKC-alpha signal transduction pathway in HEPG2 cells.Biochemical and Biophysical Research Communications 245, 254–258 (1998).PubMedCrossRefGoogle Scholar
  11. 11.
    Marino, M., Acconcia, F., Bresciani, F., Weisz, A. & Trentalance, A. Distinct nongenomic signal transduction pathways controlled by 17beta-estradiol regulate DNA synthesis and cyclin D1 gene transcription in HepG2 cells.Mol. Biol. Cell. 13, 3720–3729 (2002).PubMedCrossRefGoogle Scholar
  12. 12.
    Castoria, G.et al. Non-transcriptional action of oestradiol and progestin triggers DNA synthesis.The EMBO Journal 18, 2500–2510 (1999).PubMedCrossRefGoogle Scholar
  13. 13.
    Castoria, G.et al. PI3-kinase in concert with Src promotes the S-phase entry of oestradiol-stimulated MCF-7 cells.The EMBO Journal 20, 6050–6059 (2001).PubMedCrossRefGoogle Scholar
  14. 14.
    Lobenhofer, E. K., Huper, G., Iglehart, J. D. & Marks, J. R. Inhibition of mitogen-activated protein kinase and phosphatidylinositol 3-kinase activity in MCF-7 cells prevents estrogen-induced mitogenesis.Cell Growth Differ. 11, 99–110 (2000).PubMedGoogle Scholar
  15. 15.
    Fernando, R. I. & Wimalasena, J. Estradiol abrogates apoptosis in breast cancer cells through inactivation of BAD: ras-dependent nongenomic pathways requiring signaling through ERK and akt.Mol. Biol. Cell. 15, 3266–3284 (2004).PubMedCrossRefGoogle Scholar
  16. 16.
    Barrett, T.et al. NCBI GEO: mining millions of expression profiles-database and tools.Nucl. Acids Res. 33, D562–566 (2005).PubMedCrossRefGoogle Scholar
  17. 17.
    Edgar, R., Domrachev, M., & Lash, A. E. Gene expression omnibus: NCBI gene expression and hybridization array data repository.Nucl. Acids Res. 30, 207–210 (2002).PubMedCrossRefGoogle Scholar
  18. 18.
    Chatterjee, S. & Price, B.Regression Analysis by Example 2nd Edn (Wiley, 1991).Google Scholar
  19. 19.
    Tseng, G. C., Oh, M. K., Rohlin, L., Liao, J. C. & Wong, W. H. Issues in cDNA microarray analysis: quality filtering, channel normalization, models of variations and assessment of gene effects.Nucleic Acids Research 29, 2549–2557 (2001).PubMedCrossRefGoogle Scholar
  20. 20.
    Breitling, R., Armengaud, P., Amtmann, A. & Herzyk, P. Rank products: a simple, yet powerful, new method to detect differentially regulated genes in replicated microarray experiments.FEBS Letters 573, 83–92 (2004).PubMedCrossRefGoogle Scholar
  21. 21.
    Breitling, R. & Herzyk, P. Biological master games: using biologists’ reasoning to guide algorithm development for integrated functional genomics.Omics: A Journal of Integrative Biology 9, 225–232 (2005).CrossRefGoogle Scholar
  22. 22.
    Hong, F.et al. RankProd: a bioconductor package for detecting differentially expressed genes in meta-analysis.Bioinformatics 22, 2825–2827 (2006).PubMedCrossRefGoogle Scholar
  23. 23.
    Eyre, T. A.et al. The HUGO gene nomenclature database, 2006 updates.Nucl. Acids Res. 34, D319–321 (2006).PubMedCrossRefGoogle Scholar
  24. 24.
    Brown, K. & Jurisica, I. Unequal evolutionary conservation of human protein interactions in interologous networks.Genome Biology 8, R95 (2007).PubMedCrossRefGoogle Scholar
  25. 25.
    Huang, D. W.et al. The DAVID gene functional classification tool: a novel biological module-centric algorithm to functionally analyze large gene lists.Genome Biology 8, R183 (2007).CrossRefGoogle Scholar
  26. 26.
    Bindea, G.et al. ClueGO: a cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks.Bioinformatics 25, 1091–1093 (2009).PubMedCrossRefGoogle Scholar
  27. 27.
    Lin, C.et al. Discovery of estrogen receptor alpha target genes and response elements in breast tumor cells.Genome Biology 5, R66 (2004).PubMedCrossRefGoogle Scholar
  28. 28.
    Stossi, F.et al. Transcriptional profiling of estrogen-regulated gene expression via estrogen receptor (ER)α or ERβ in human osteosarcoma cells: distinct and common target genes for these receptors.Endocrinology 145, 3473–3486 (2004).PubMedCrossRefGoogle Scholar

Copyright information

© The Korean Society of Environmental Risk Assessment and Health Science and Springer 2010

Authors and Affiliations

  • Won Cheol Yim
    • 1
  • Changwon Keum
    • 2
  • Saehwan Kim
    • 3
  • Yeojeong Cho
    • 4
  • Byung-Moo Lee
    • 1
  • Yongeun Kwon
    • 4
  1. 1.Department of Plant BiotechnologyDongguk Univ-SeoulSeoulKorea
  2. 2.Bioinformatics and Molecular Design Research Center (BMDRC)SeoulKorea
  3. 3.MacrogenSeoulKorea
  4. 4.Department of Medical BiotechnologyDongguk Univ-SeoulSeoulKorea

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