Skip to main content

Advertisement

Log in

GGCn polymorphism of eRF3a/GSPT1 gene and breast cancer susceptibility

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

The significance of translation regulatory factors in elevating the risk of cancer has been recently recognized. Eukaryotic release factor 3a (eRF3a) is a translation termination protein that is encoded by G1 to S phase transition 1 gene (GSPT1). The eRF3a/GSPT1 exon 1 contains a trinucleotide GGC repeat coding for a polyglycine expansion in the N-terminal of the protein. In the present study, we determined the allelic length of the GGCn repeat in the eRF3a gene in 250 women with breast cancer and 250 age-matched controls. Our results show that the presence of the longer allele, 12-GGC, is correlated with threefold increased risk of breast cancer development. Our findings also suggest that women who are homozygous for 7-GGC allele are possibly at higher risk of developing breast cancer, especially before the age of 50. No significant effect of the allelic length of eRF3a/GSPT1 polymorphism on inheritance or the grade of this disease was observed.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Bray F, McCarron P, Parkin DM. The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res. 2004;6:229–39.

    Article  PubMed  Google Scholar 

  2. Johnson N, Dickson-Swift V. It usually happens in older women: young women’s perceptions about breast cancer. Health Educ J. 2008;67(4):243–57.

    Article  Google Scholar 

  3. Harirchi I, Ebrahimi M, Zamani N, Jarvandi S, Montazeri A. Breast cancer in Iran: a review of 903 case records. Public Health. 2000;114:143–5.

    PubMed  CAS  Google Scholar 

  4. Mousavi SM, Montazeri MA, Mousavi Jarrahi A, Harirchi I, Najafi M, Ebrahimi M. Breast cancer in Iran: an epidemiological review. Breast J. 2007;13:383–91.

    Article  PubMed  Google Scholar 

  5. Zhouravleva G, Frolova L, Le Goff X, et al. Termination of translation in eukaryotes in governed by two interacting polypeptide chain release factors, eRF1and eRF3. EMBO J. 1995;14:4065–72.

    PubMed  CAS  Google Scholar 

  6. Hoshino S, Hosoda N, Araki T, et al. Novel function of the eukaryotic polypeptide-chain releasing factor 3 (eRF3/GSPT) in the mRNA degradation pathway. Biochemistry. 1999;64(12):1367–72.

    PubMed  CAS  Google Scholar 

  7. Hoshino S, Ima M, Mizutani M, et al. Molecular cloning of the eukaryotic polypeptide releasing factors (eRF): its identification as eRF3 interacting with eRF1. J Biol Chem. 1998;273:22254–9.

    Article  PubMed  CAS  Google Scholar 

  8. Chauvin C, Salhi S, Jean–Jean O. Human eukaryotic release factor 3a depletion causes cell cycle arrest at G1 phase through inhibition of the mTOR pathway. Mol Cell Biol. 2007;27:5619–29.

    Article  PubMed  CAS  Google Scholar 

  9. Valouev IA, Kushnirov VV, Tre-Avanesyan MD. Yeast polypeptide chain release factors eRF1and eRF3 are involved in cytoskeleton organization and cell cycle regulation. Cell Motil Cytoskeleton. 2002;52:161–73.

    Article  PubMed  CAS  Google Scholar 

  10. Lee JA, Park JE, Lee DH, et al. G1 to S phase transition protein 1 induces apoptosis signal-regulating kinase1 activation by dissociating 14–3-3 from ASK1. Oncogene. 2008;27:1297–305.

    Article  PubMed  CAS  Google Scholar 

  11. Hedge R, Srinivasula SM, Datta P, et al. The polypeptide chain-releasing factor GSPT1/eRF3 is proteolytically processed into an IAP-binding protein. J Biol Chem. 2003;278:38699–706.

    Article  Google Scholar 

  12. Ozawa K, Murakami Y, Eki T, Yokoyama K, et al. Mapping of the human GSPT1 gene, a human homolog of the yeast GST1 gene, to chromosomal band 16p13.1. Somat Cell Mol Genet. 1992;18:189–94.

    Article  PubMed  CAS  Google Scholar 

  13. Hansen LL, Jakobsen CG, Justesen J. Assignment of the human peptide chain release factor 3 (GSPT2) to Xp11.23Rp11.21 and of the distal marker DXS1039 by radiation hybrid mapping. Cytogenet Cell Genet. 1999;86:250–1.

    Article  PubMed  CAS  Google Scholar 

  14. Chauvin C, Salhi S, Le Goff W, et al. Involvement of human release factors eRF3a and eRF3b in translation termination and regulation of the termination complex formation. Mol Cell Biol. 2005;25:5801–11.

    Article  PubMed  CAS  Google Scholar 

  15. Brito M, Malta-Vacas J, Carmona B, et al. Polyglycine expansions in eRF3/GSPT1 are associated with gastric cancer susceptibility. Carcinogenesis. 2005;26:2046–9.

    Article  PubMed  CAS  Google Scholar 

  16. Malta-Vacas J, Chauvin C, Gonçalves L, et al. eRF3a/GSPT1 12-GGC allele increases the susceptibility for breast cancer development. Oncol Rep. 2009;21:1551–8.

    PubMed  CAS  Google Scholar 

  17. Malta-Vacas J, Ferreira P, Monterio C, Brito M. Differential expression of GSPT1 GGC n alleles in cancer. Cancer Genet Cytogenet. 2009;195:132–42.

    Article  PubMed  CAS  Google Scholar 

  18. Tallheden T, Karlsson C, Brunner A. Gene expression during redifferentiation of human articular chondrocytes. Osteoarthr Cartil. 2004;12:225–35.

    Article  Google Scholar 

  19. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.

    Article  PubMed  CAS  Google Scholar 

  20. Basu J, Williams BC, Li Z, Williams EV, Goldberg ML. Depletion of a Drosophila homolog of yeast Sup35p disrupts spindle assembly, chromosome segregation, and cytokinesis during male meiosis. Cell Motil Cytoskeleton. 1998;39:286–302.

    Article  PubMed  CAS  Google Scholar 

  21. Eastmond DA, Tucker JD. Identification of aneuploidy-inducing agents using cytokinesis-blocked human lymphocytes, and an antikinetochore antibody. Environ Mol Mutagen. 1989;13:34–43.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to thank all patients who contributed to this investigation and Professor Farzin Farzaneh (Kings College London) for valuable suggestions and critical reading of this manuscript. This work was supported by University of Isfahan.

Conflicts of interest

The authors report no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Manoochehr Tavassoli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miri, M., Hemati, S., Safari, F. et al. GGCn polymorphism of eRF3a/GSPT1 gene and breast cancer susceptibility. Med Oncol 29, 1581–1585 (2012). https://doi.org/10.1007/s12032-011-0111-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-011-0111-x

Keywords

Navigation