Skip to main content
SpringerLink
Log in

Contribution of Aurora-A and -B expression to DNA aneuploidy in gastric cancers

  • Original Article
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

Purpose

DNA aneuploidy, which is characterized by cells containing an abnormal number of chromosomes, is closely associated with carcinogenesis and malignant progression. Aneuploidy occurs during cell division when the chromosomes do not separate properly. Aurora kinases (Aurora-A, -B, and -C) contribute to accurate cell division, and are candidate molecular targets for mitosis-specific anticancer drugs.

Methods

We determined the expression of Aurora-A and -B in 110 gastric cancer specimens by performing an immunohistochemical analysis. We also determined the DNA content, TP53 gene mutations, and microsatellite instability in the same samples.

Results

We found the nuclear expression of Aurora-A and -B to increase in tumor tissue in comparison to that in normal epithelial tissue. A high Aurora-B expression significantly correlated with aneuploidy and TP53 mutations, but not with microsatellite instability. In contrast, the Aurora-A expression did not correlate with either aneuploidy or microsatellite instability. In addition, the expression of Aurora-A or -B was not significantly associated with the clinical outcomes or prognosis.

Conclusions

Our results suggest that an overexpression of Aurora-B, but not of Aurora-A, might contribute to DNA aneuploidy in gastric cancers by promoting chromosomal instability.

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
Fig. 3

Similar content being viewed by others

References

  1. Thompson SL, Compton DA. Examining the link between chromosomal instability and aneuploidy in human cells. J Cell Biol. 2008;180:665–72.

    Article  CAS  PubMed  Google Scholar 

  2. Thompson SL, Bakhoum SF, Compton DA. Mechanisms of chromosomal instability. Curr Biol. 2010;20:R285–95.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Schvartzman JM, Sotillo R, Benezra R. Mitotic chromosomal instability and cancer: mouse modelling of the human disease. Nat Rev Cancer. 2010;10:102–15.

    Article  CAS  PubMed  Google Scholar 

  4. Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature. 1998;396:643–9.

    Article  CAS  PubMed  Google Scholar 

  5. Yamashita K, Sakuramoto S, Watanabe M. Genomic and epigenetic profiles of gastric cancer: potential diagnostic and therapeutic applications. Surg Today. 2011;41:24–38.

    Article  PubMed  Google Scholar 

  6. Pellman D. Cell biology: aneuploidy and cancer. Nature. 2007;446:38–9.

    Article  CAS  PubMed  Google Scholar 

  7. Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology. 2010;138(2073–2087):e2073.

    Article  Google Scholar 

  8. Tokunaga E, Oki E, Oda S, et al. Frequency of microsatellite instability in breast cancer determined by high-resolution fluorescent microsatellite analysis. Oncology. 2000;59:44–9.

    Article  CAS  PubMed  Google Scholar 

  9. Albertson DG, Collins C, McCormick F, Gray JW. Chromosome aberrations in solid tumors. Nat Genet. 2003;34:369–76.

    Article  CAS  PubMed  Google Scholar 

  10. Sen S. Aneuploidy and cancer. Curr Opin Oncol. 2000;12:82–8.

    Article  CAS  PubMed  Google Scholar 

  11. Sjoblom T, Jones S, Wood LD, et al. The consensus coding sequences of human breast and colorectal cancers. Science. 2006;314:268–74.

    Article  PubMed  Google Scholar 

  12. Ando K, Kakeji Y, Kitao H, et al. High expression of BUBR1 is one of the factors for inducing DNA aneuploidy and progression in gastric cancer. Cancer Sci. 2010;101:639–45.

    Article  CAS  PubMed  Google Scholar 

  13. Cahill DP, Lengauer C, Yu J, et al. Mutations of mitotic checkpoint genes in human cancers. Nature. 1998;392:300–3.

    Article  CAS  PubMed  Google Scholar 

  14. Lens SM, Voest EE, Medema RH. Shared and separate functions of polo-like kinases and aurora kinases in cancer. Nat Rev Cancer. 2010;10:825–41.

    Article  CAS  PubMed  Google Scholar 

  15. Holland AJ, Cleveland DW. Boveri revisited: chromosomal instability, aneuploidy, and tumorigenesis. Nat Rev Mol Cell Biol. 2009;10:478–87.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Barr AR, Gergely F. Aurora-A: the maker and breaker of spindle poles. J Cell Sci. 2007;120:2987–96.

    Article  CAS  PubMed  Google Scholar 

  17. Vader G, Medema RH, Lens SM. The chromosomal passenger complex: guiding Aurora-B through mitosis. J Cell Biol. 2006;173:833–7.

    Article  CAS  PubMed  Google Scholar 

  18. Ditchfield C, Johnson VL, Tighe A, et al. Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J Cell Biol. 2003;161:267–80.

    Article  CAS  PubMed  Google Scholar 

  19. Yuan B, Xu Y, Woo JH, et al. Increased expression of mitotic checkpoint genes in breast cancer cells with chromosomal instability. Clin Cancer Res. 2006;12:405–10.

    Article  CAS  PubMed  Google Scholar 

  20. Enjoji M, Iida S, Sugita H, et al. BubR1 and AURKB overexpression are associated with a favorable prognosis in gastric cancer. Mol Med Report. 2009;2:589–96.

    CAS  Google Scholar 

  21. Tatsuka M, Katayama H, Ota T, et al. Multinuclearity and increased ploidy caused by overexpression of the aurora- and Ipl1-like midbody-associated protein mitotic kinase in human cancer cells. Cancer Res. 1998;58:4811–6.

    CAS  PubMed  Google Scholar 

  22. Jass JR SL. Histological typing of intestinal tumours. WHO International Histological Classification of Tumours No. 15. 2nd ed. Berlin: Springer. 1989.

  23. Sobin LH WC, editors. TNM Classification of malignant tumours, 6th ed. New York: Wiley–Liss. 2002.

  24. Chieffi P, Cozzolino L, Kisslinger A, et al. Aurora B expression directly correlates with prostate cancer malignancy and influence prostate cell proliferation. Prostate. 2006;66:326–33.

    Article  CAS  PubMed  Google Scholar 

  25. Kamada T, Sasaki K, Tsuji T, et al. Sample preparation from paraffin-embedded tissue specimens for laser scanning cytometric DNA analysis. Cytometry. 1997;27:290–4.

    Article  CAS  PubMed  Google Scholar 

  26. Sasaki K, Kurose A, Miura Y, et al. DNA ploidy analysis by laser scanning cytometry (LSC) in colorectal cancers and comparison with flow cytometry. Cytometry. 1996;23:106–9.

    Article  CAS  PubMed  Google Scholar 

  27. Furuya T, Uchiyama T, Murakami T, et al. Relationship between chromosomal instability and intratumoral regional DNA ploidy heterogeneity in primary gastric cancers. Clin Cancer Res. 2000;6:2815–20.

    CAS  PubMed  Google Scholar 

  28. Hiddemann W, Schumann J, Andreef M, et al. Convention on nomenclature for DNA cytometry. Committee on nomenclature, society for analytical cytology. Cancer Genet Cytogenet. 1984;13:181–3.

    Article  CAS  PubMed  Google Scholar 

  29. Oki E, Hisamatsu Y, Ando K, et al. Clinical aspect and molecular mechanism of DNA aneuploidy in gastric cancers. J Gastroenterol. 2012;47:351–8.

    Article  PubMed  Google Scholar 

  30. Brenner BM, Rosenberg D. High-throughput SNP/CGH approaches for the analysis of genomic instability in colorectal cancer. Mutat Res. 2010;693:46–52.

    Article  CAS  PubMed  Google Scholar 

  31. Oda S, Oki E, Maehara Y, Sugimachi K. Precise assessment of microsatellite instability using high resolution fluorescent microsatellite analysis. Nucleic Acids Res. 1997;25:3415–20.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Baba H, Korenaga D, Kakeji Y, et al. DNA ploidy and its clinical implications in gastric cancer. Surgery. 2002;131:S63–70.

    Article  PubMed  Google Scholar 

  33. Doak SH. Aneuploidy in upper gastro-intestinal tract cancers—a potential prognostic marker? Mutat Res. 2008;651:93–104.

    Article  CAS  PubMed  Google Scholar 

  34. Duensing A, Duensing S. Guilt by association? p53 and the development of aneuploidy in cancer. Biochem Biophys Res Commun. 2005;331:694–700.

    Article  CAS  PubMed  Google Scholar 

  35. Fichter CD, Herz C, Munch C, et al. Occurrence of multipolar mitoses and association with Aurora-A/-B kinases and p53 mutations in aneuploid esophageal carcinoma cells. BMC Cell Biol. 2011;12:13.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Meraldi P, Honda R, Nigg EA. Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53−/− cells. EMBO J. 2002;21:483–92.

    Article  CAS  PubMed  Google Scholar 

  37. Baba Y, Nosho K, Shima K, et al. Aurora-A expression is independently associated with chromosomal instability in colorectal cancer. Neoplasia. 2009;11:418–25.

    CAS  PubMed Central  PubMed  Google Scholar 

  38. Wang X, Zhou YX, Qiao W, et al. Overexpression of aurora kinase A in mouse mammary epithelium induces genetic instability preceding mammary tumor formation. Oncogene. 2006;25:7148–58.

    Article  CAS  PubMed  Google Scholar 

  39. Lassus H, Staff S, Leminen A, et al. Aurora-A overexpression and aneuploidy predict poor outcome in serous ovarian carcinoma. Gynecol Oncol. 2011;120:11–7.

    Article  CAS  PubMed  Google Scholar 

  40. Sakakura C, Hagiwara A, Yasuoka R, et al. Tumour-amplified kinase BTAK is amplified and overexpressed in gastric cancers with possible involvement in aneuploid formation. Br J Cancer. 2001;84:824–31.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Ota T, Suto S, Katayama H, et al. Increased mitotic phosphorylation of histone H3 attributable to AIM-1/Aurora-B overexpression contributes to chromosome number instability. Cancer Res. 2002;62:5168–77.

    CAS  PubMed  Google Scholar 

  42. Chen YJ, Chen CM, Twu NF, et al. Overexpression of Aurora B is associated with poor prognosis in epithelial ovarian cancer patients. Virchows Arch. 2009;455:431–40.

    Article  CAS  PubMed  Google Scholar 

  43. Burum-Auensen E, DeAngelis PM, Schjolberg AR, et al. Reduced level of the spindle checkpoint protein BUB1B is associated with aneuploidy in colorectal cancers. Cell Prolif. 2008;41:645–59.

    Article  CAS  PubMed  Google Scholar 

  44. Kulkarni AA, Loddo M, Leo E, et al. DNA replication licensing factors and aurora kinases are linked to aneuploidy and clinical outcome in epithelial ovarian carcinoma. Clin Cancer Res. 2007;13:6153–61.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to Ms. Yoko Kubota for her valuable technical assistance.

Conflict of interest

Hiroyuki Kitao and other co-authors have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Kenichi Honma, Ryota Nakanishi, Tomonori Nakanoko, Koji Ando, Hiroshi Saeki, Eiji Oki, Yoshihiro Kakeji & Yoshihiko Maehara

  2. Department of Molecular Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Ryota Nakanishi, Makoto Iimori & Hiroyuki Kitao

Authors
  1. Kenichi Honma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ryota Nakanishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tomonori Nakanoko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Koji Ando
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroshi Saeki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eiji Oki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Makoto Iimori
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hiroyuki Kitao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yoshihiro Kakeji
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yoshihiko Maehara
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroyuki Kitao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Honma, K., Nakanishi, R., Nakanoko, T. et al. Contribution of Aurora-A and -B expression to DNA aneuploidy in gastric cancers. Surg Today 44, 454–461 (2014). https://doi.org/10.1007/s00595-013-0581-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00595-013-0581-x

Keywords

Search

Navigation