Skip to main content
SpringerLink
Log in

Altered gene expression and functions in thalidomide-treated human placenta choriocarcinoma (JEG-3) cells

  • Original Research
  • Published:
BioChip Journal Aims and scope Submit manuscript

Abstract

Thalidomide is a sedative, hypnotic, and anti-inflammatory medicine. However, exposure during the pregnancy is known to cause several developmental disorders. The most fearful side-effects are teratogenicity and neuropathy. Development is a highly coordinated set of processes that depend on hierarchies of signaling and gene regulatory networks, and the disruption of such networks may underlie many cases of chemically induced birth defects. In this research, we compared the global gene expression responses by thalidomide in human placenta choriocarcinoma cell line (JEG-3) by using agilent human whole genome chip. Through the analysis of gene expression profiles, we identified 167 up-regulated genes and 56 down-regulated genes changed by thalidomide by more than 1.5-fold. And also functions related to genes expressed by thalidomide were apoptosis, angiogenesis, and cell adhesion. In summary, we examined genes and functions associated with teratogenic effects of thalidomide using global expression profiling and functional analysis. Thus, our data suggest that thalidomide may block angiogenesis signal pathway through inactivation of cell adhesion, and these anti-angiogenesis may be affected limb development.

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

Similar content being viewed by others

References

  1. Sauer, H., Gunther, J., Hescheler, J. & Wartenberg, M. Thalidomid inhibits angiogenesis in embryoid bodies by the generation of hydroxyl radicals. Am. J. Pathol. 156, 151–158 (2000).

    CAS  Google Scholar 

  2. McBride, W.G. Thalidomide and congenital abnormalities. Lancet 2, 1358 (1961).

    Article  Google Scholar 

  3. Lenz, W. & Knapp, K. Thalidomide embryopathy. Arch. Environ. Health 5, 100–105 (1962).

    CAS  Google Scholar 

  4. Breitkreutz, I. & Anderson, K.C. Thalidomide in multiple myeloma-clinical trials and aspects of drug metabolism and toxicity. Expert Opin. Drug Metab. Toxicol. 4, 973–985 (2008).

    Article  CAS  Google Scholar 

  5. Zeldis, J.B., Williams, B.A., Thomas, S.D. & Elsayed, M.E. S.T.E.P.S.: A comprehensive program for controlling and monitoring access to thalidomide. Clin. Ther. 21, 319–330 (1999).

    Article  CAS  Google Scholar 

  6. Stephens, T.D. & Fillmore, B.J. Hypothesis: thalidomide embryopathy-proposed mechanism of action. Teratology 61, 189–195 (2000).

    Article  CAS  Google Scholar 

  7. Meise, W., Ockenfels, H. & Köhler, F. Teratologische prufung der hydrolysenprodukte des thalidomids. Experientia 29, 423–424 (1973).

    Article  CAS  Google Scholar 

  8. Kenyon, B.M., Browne, F. & D’Amato, R.J. Effects of thalidomide and related metabolites in a mouse corneal model of neovascularization. Exp. Eye. Res. 64, 971–978 (1997).

    Article  CAS  Google Scholar 

  9. Kim, Y.J. et al. Differential gene expression induced by naphthalene in two human cell line, HepG2 and HL-60. Mol. Cell. Toxicol. 5, 99–107 (2009).

    CAS  Google Scholar 

  10. Bae, H.J. et al. Decreased expression of the suppressor of cytokine signaling 6 in human hepatocellular carcinoma. Mol. Cell. Toxicol. 5, 193–197 (2009).

    Google Scholar 

  11. Reynolds, L.P. & Redmer, D.A. Angiogenesis in the placenta. Biol. Reprod. 64, 1033–1040 (2001).

    Article  CAS  Google Scholar 

  12. Geduspan, J.S. & Solursh, M. Effects of the mesonephros and insulin-like growth factor-I on chondrogenesis of limb explants. Devl. Biol. 156, 500–508 (1993).

    Article  CAS  Google Scholar 

  13. Dealy, C.N. & Kosher, R.A. IGF-I, insulin and FGFs induce outgrowth of the limb buds of amelic mutant chick embryos. Development 122, 1323–1330 (1996).

    CAS  Google Scholar 

  14. Bischoff, J. Cell adhesion and angiogenesis. J. Clin. Invest. 99, 373–376 (1997).

    Article  CAS  Google Scholar 

  15. Stephens, T.D., Bunde, C.J. & Fillmore, B.J. Mechanism of action in thalidomide teratogenesis. Biochem. Pharmacol. 59, 1489–1499 (2000).

    Article  CAS  Google Scholar 

  16. Beauvais, D.M., Ell, B.J., McWhorter, A.R. & Rapraeger, A.C. Syndecan-1 regulates alphavbeta3 and alphavbeta5 integrin activation during angiogenesis and is blocked by synstatin, a novel peptide inhibitor. J. Exp. Med. 206, 691–705 (2009).

    Article  CAS  Google Scholar 

  17. Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55–63 (1983).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul, 130-650, Korea

    Youn-Jung Kim, Jina Lee & Jae-Chun Ryu

Authors
  1. Youn-Jung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jina Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jae-Chun Ryu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jae-Chun Ryu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, YJ., Lee, J. & Ryu, JC. Altered gene expression and functions in thalidomide-treated human placenta choriocarcinoma (JEG-3) cells. BioChip J 4, 22–29 (2010). https://doi.org/10.1007/s13206-010-4104-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13206-010-4104-1

Keywords

Search

Navigation