IMMUNOHISTOCHEMICAL STUDY OF AURORA-2 KINASE IN THE ORAL SQUAMOUS CELL CARCINOMA

구강편평상피암종에서 Aurora-2 kinase 발현에 대한 면역조직화학적 연구

  • Han, Se-Jin (Department of Oral and Maxillofacial Surgery, College of Dentistry, Dankook University) ;
  • Kim, Se-Woong (Department of Oral and Maxillofacial Surgery, College of Dentistry, Dankook University) ;
  • Kim, Kyung-Wook (Department of Oral and Maxillofacial Surgery, College of Dentistry, Dankook University)
  • 한세진 (단국대학교 치과대학 구강악안면외과학교실) ;
  • 김세웅 (단국대학교 치과대학 구강악안면외과학교실) ;
  • 김경욱 (단국대학교 치과대학 구강악안면외과학교실)
  • Received : 2009.11.12
  • Accepted : 2010.02.05
  • Published : 2010.03.31

Abstract

Aurora kinases represent a novel family of serine/threonine kinases crucial for cell cycle control. Aurora-2 kinase is mainly involved in centrosome function, mitotic entry, and spindle assembly. Aurora-2 kinase overexpression causes centrosome amplification and the formation of multipolar mitotic spindles, which leads to tumor aneuploidy and so it has been found to play an important role in tumorigenicity in many cancers such as colorectal cancer, breast cancer and cervical cancer. Hence, the goal of this study is to identify the correlation of clinicopathlogical factors and overexpression of Aurora-2 kinase in oral squamous cell carcinoma. We studied the immunohistochemical staining of Aurora-2 kinase in 20 specimens of 20 patients with oral squamous cell carcinoma and the relationships between Aurora-2 kinase over expression and each of the clinico-pathological parameters were analyzed by Pearson correlation analysis. Statistical significance was set at P < 0.05. The results were as follows. 1. In the immunohistochemical study of poorly differentiated and invasive oral squamous cell carcinoma, the high level staining of Aurora-2 kinase was observed. 2. The correlation between immunohistochemical Aurora-2 kinase expression and histopathological differentiation of specimens was significant. These findings suggest that overexpression of Aurora-2 kinase may play a important role in carcinogenesis of oral squamous cell carcinoma.

Keywords

References

  1. Mao L, Hong WK, Papadimitrakopoulou VA : Focus on head and neck cancer. Cancer Cell 5 : 311, 2004. https://doi.org/10.1016/S1535-6108(04)00090-X
  2. Jemal A, Siegel R, Ward E et al : Cancer statistics. CA Cancer J Clin 56 : 106, 2006. https://doi.org/10.3322/canjclin.56.2.106
  3. Freier K, Bosch FX, Flechtenmacher C et al : Distinct site-specific oncoprotein overexpression in head and neck squamous cell carcinoma: a tissue microarray analysis. Anticancer Res 23 : 3971, 2003.
  4. Vogelstein B, Kinzler KW : The multistep nature of cancer. Trends Genet. 1993, p.138.
  5. Schoell WMJ, Janicek MR, Mirhashemi R : Epidemiology and biology of cervical cancer. Semin Surg Oncol 16 : 1999.
  6. Rubin Grandis J, Melhem MF, Gooding WE : Levels of TGF-alpha and EGFR protein in head and neck squamous cell carcinoma and patient survival. J Natl Cancer lnst 90 : 824, 1998. https://doi.org/10.1093/jnci/90.11.824
  7. Maurizi M, Almadori G, Ferrandina G et al : Prognostic significance of epidermal growth factor receptor in laryngeal squamous cell carcinoma. Brit J Cancer 74 : 1253, 1996. https://doi.org/10.1038/bjc.1996.525
  8. Sathyan KM, Nalinakumari KR, Abraham T : Influence of single nucleotide polymorphisms in H-Ras and eyclin D1 genes on oral cancer susceptibility. Oral Oncol 42 : 607, 2006. https://doi.org/10.1016/j.oraloncology.2005.10.019
  9. Auerkari El : Methylation of tumor suppressor genes p16(lNK4a), p27(Kip1) and E-cadherin in carcinogenesis. Oral Oncol 42 : 5, 2006. https://doi.org/10.1016/j.ooe.2005.05.007
  10. Wang L, Liu T, Nishioka M : Activation of ERK1/2 and cyelin D1 expression in oral tongue squamous cell carcinomas: relationship between clinicopathological appearances and cell proliferation. Oral Oncol 42 : 625 2006. https://doi.org/10.1016/j.oraloncology.2005.11.002
  11. He Y, Zeng Q, Drenning SD et al : Inhibition of human squamous cell carcinoma growth in vivo by epidermal growth factor receptor antisense RNA transcribed from the U6 promoter. J Natl Cancer Inst 90 : 1080, 1998. https://doi.org/10.1093/jnci/90.14.1080
  12. Caponigro F, Milano A, Basile M : Recent advances in head and neck cancer therapy: the role of new cytotoxic and molecular-targeted agents. Curr Opin Oncol 18 : 247, 2006. https://doi.org/10.1097/01.cco.0000219253.53091.fb
  13. Glover DM, Leibowitz MH, McLean DA : Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles. Cell 81 : 95, 1995. https://doi.org/10.1016/0092-8674(95)90374-7
  14. Schumacher JM, Ashcroft N, Donovan PJ : A highly can served centrosomal kinase, AIR-1, is required for accurate cell cycle progression and segregation of developmental factors in Caenorhabditis elegans embryos. Development 125 : 4391, 1998.
  15. Schumacher JM, Golden A, Donovan PJ : AIR-2:An Aurora/Ipl1-related protein kinase associated with chromosomes and midbody microtubules is required for polar body extrusion and cytokinesis in Caenorhabditis elegans embryos. J Cell BioI 143 : 1635, 1998. https://doi.org/10.1083/jcb.143.6.1635
  16. Mesilaty-Gross S, Reich A. Motro B : The Drosophila STAM gene homolog is in a tight gene cluster. and its expression correlates to that of the adjacent gene ial. Gene 231 : 173, 1999. https://doi.org/10.1016/S0378-1119(99)00053-0
  17. Roghi C, Giet R, Uzbekov R : The Xenopus protein kinase pEg2 associates with the centrosome in a cell cycle-dependent manner, binds to the spindle microtubules and is involved in bipolar mitotic spindle assembly. J Cell Sci 111 : 557, 1998.
  18. Adams RR, Wheatley SP, Gouldsworthy AM et al : INCENP binds the Aurora-related kinase AIRK2 and is required to target it to chromosomes, the central spindle and cleavage furrow. Curr Biol 10 : 1075, 2000. https://doi.org/10.1016/S0960-9822(00)00673-4
  19. Nigg EA : Mitotic kinases as regulators of cell division and its checkpoints. Nat Rev Mol Cell BioI 2 : 21, 2001.
  20. Marumoto T. Honda S, Hara T : Aurora-A kinase maintains the fidelity of early and late mitotic events in HeLa cells. J Biol Chem 278 : 51786, 2003. https://doi.org/10.1074/jbc.M306275200
  21. Sen S. Zhou H. White RA : A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines. Oncogene 14 : 2195. 1997. https://doi.org/10.1038/sj.onc.1201065
  22. Tanner M, Grenman S, Koul A et al : Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer. Clin. Cancer Res. 6 : 1833, 2000.
  23. Harrington EA, Bebbington D, Moore J : VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med 10 : 262, 2004. https://doi.org/10.1038/nm1003
  24. Ditchfield C, Johnson VL, Tighe A : Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J Cell BioI 161 : 267, 2003. https://doi.org/10.1083/jcb.200208091
  25. Mitelman F, Johansson B, Mertens F : Catalog of Chromosome Aberrations in Cancer. New York, Wiley-Liss, 1994, p.11.
  26. Zhou B, Elledge SJ : The DNA damage response: putting checkpoints in perspective. Nature (Lond.) 408 : 433, 2000. https://doi.org/10.1038/35044005
  27. CW Lee : Cell cycle checkpoint control. Exp. Mol. Med 33 : 39, 2001.
  28. Sakai H : Microtubules in mitosis. Cell Struct. Funct 19 : 57, 1994. https://doi.org/10.1247/csf.19.57
  29. Kellogg DR, Moritz M, Alberts BM : The centrosome and cellular organization. Annu. Rev. Biochem 63 : 639, 1994. https://doi.org/10.1146/annurev.bi.63.070194.003231
  30. Bayliss R, Sardon T, Vernos I : Structural basis or Aurora-A activation by TPX2 at the mitotic spindle. Mol Cell 12 : 851, 2003. https://doi.org/10.1016/S1097-2765(03)00392-7
  31. Fu J, Bian M, Jiang Q : Roles of Aurora Kinases in Mitosis and Tumorigenesis. Mol Cancer Res 5 : 1, 2007. https://doi.org/10.1158/1541-7786.MCR-06-0208
  32. Meraldi P, Honda R, Nigg EA : Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53/ cells. EMBO J 21 : 483, 2002. https://doi.org/10.1093/emboj/21.4.483
  33. Anand S, Penrhyn-Lowe S, Venkitaraman AR : AURORA-A amplification overrides the mitotic spindle assembly checkpoint. inducing resistance to Taxol. Cancer Cell 3 : 51, 2003. https://doi.org/10.1016/S1535-6108(02)00235-0
  34. Katayama H, Sasai K, Kawai H : Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat Genet 36 : 55, 2004. https://doi.org/10.1038/ng1279
  35. Twu NF, Yuan CC, Yen MS et al : Expression of Aurora kinase A and B in normal and malignant cervical tissue: high Aurora A kinase expression in squamous cervical cancer. Eur J Obstet Gynecol Reprod BioI 142 : 57, 2009. https://doi.org/10.1016/j.ejogrb.2008.09.012