Abstract
Aurora-B kinase is a chromosomal passenger protein and is essential for chromosome segregation and cytokinesis. Aurora-B overexpression in various cancer cells induces chromosomal number instability to produce multinuclearity and relates to metastasis. Here, we examined the expression of Aurora-B in oral squamous cell carcinoma (OSCC) to elucidate the relationship between Aurora-B expression and clinico-pathological findings by immunohistochemistry. Aurora-B expression was observed in normal oral squamous epithelia and OSCC cases, but the number of positive cells was significantly higher in OSCC than in normal squamous epithelium (p < 0.01). The labeling index of Aurora-B was significantly correlated with lymph node metastasis (p < 0.01) and histological grades of differentiation (p < 0.01). We also compared Aurora-B expression with Ki-67 expression and a positive correlation was found (p < 0.0001). Moreover, Aurora-B expression is significantly more frequent in multinuclear tumor cells than in total tumor cells. In summary, we found that Aurora-B expression was well correlated with cell proliferation, induction of multinuclear cells, histological differentiation, and metastasis in OSCC. These findings suggest that Aurora-B may be involved in tumor progression and that Aurora-B can be a new diagnostic and therapeutic target for OSCC.
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References
Adams RR, Carmena M, Earnshaw WC (2001) Chromosomal passengers and the (aurora) ABCs of mitosis. Trends Cell Biol 11:49–54
Adams RR, Eckley DM, Vagnarelli P, Wheatlev S, Gerloff DL, Mackav AM, Svinqen PA, Kaufmann SH, Earnshaw WC (2001) Human INCENP colocalizes with the Aurora-B/AIRK2 kinase on chromosomes and is overexpressed in tumour cells. Chromosome 110:65–74
Adams RR, Maiato H, Earnshaw WC, Carmena M (2001) Essential roles of Drosophila inner centromere protein (INCENP) and aurora B in histone H3 phosphorylation, metaphase chromosome alignment, kinetochore disjunction, and chromosome segregation. J Cell Biol 153:865–880
Beardmore VA, Ahonen LJ, Kallio MJ (2004) Survivin dynamics increases at centromeres during G2/M phase transition and is regulated by microtubule-attachment and Aurora B kinase activity. J Cell Sci 117:4033–4042
Bolton MA, Lan W, Powers SE, McCleland ML, Kuang J, Stukenberg PT (2002) Aurora B kinase exists in a complex with survivin and INCENP and its kinase activity is stimulated by survivin binding and phosphorylation. Mol Biol Cell 13:3064–3077
Chieffi P, Troncone G, Caleo A, Libertini S, Linardopoulos S, Tramontano D, Portella G (2004) Aurora B expression in normal testis and seminomas. J Endocrinol 181:263–270
Delaval B, Ferrand A, Conte N, Larroque C, Hernandez-Verdun D, Prigen C, Birnbaum D (2004) Aurora B-TACC1 protein complex in cytokinesis. Oncogene 23:4516–4522
Gassmann R, Carvalho A, Henzing AJ, Rucchaud S, Hudson DF, Honda R, Niqq EA, Gerloff DL, Earnshaw WC (2001) Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle. J Cell Biol 166:179–191
Giet R, Glover DM (2001) Drosophila Aurora-B kinase is required for Histone H3 phosphorylation and Condesin recruitment during chromosome condensation and to organize central spindle during cytokinesis. J Cell Biol 152:669–681
Hsu JY, Sun ZW, Li X, Reuben M, Tatchell K, Bishop DK, Grushcow JM, Brame CJ, Caldwell JA, Hunt DF, Lin R, Smith MM, Allis CD (2000) Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes. Cell 102:279–291
Jung JK, Kim TK, Lee JS, Oh SY, Kwak S, Jin X, Sohn JY, Song MK, Sohn YW, Lee JB, Chung YG, Choi YK, You S, Kim H (2005) Survivin inhibits anti-growth effect of p53 activated by aurora B. Biochem Biophys Res Commun 336:1164–1171
Kaitna S, Pasierbek P, Jantsch M, Loidl J, Glotzer M (2002) The aurora B kinase AIR-2 regulates kinetochores during mitosis and is required for separation of homologous chromosomes during meiosis. Curr Biol 12:798–812
Kanda A, Kawai H, Suto S, Kitajima S, Sato S, Takata T, Tatsuka M (2005) Aurora-B/AIM-1 kinase activity is involved in Ras-mediated cell transformation. Oncogene 24:7266–7272
Katayama H, Ota T, Jisaki F, Ueda Y, Tanaka T, Odashima S, Suzuki F, Terada Y, Tatsuka M (1999) Mitotic kinase expression and colorectal cancer progression. J Natl Cancer Inst 91:1160–1162
Kurai M, Shiozawa T, Shih HC (2005) Expression of Aurora kinases A and B in normal, hyperplastic, and malignant human endometrium: Aurora B as a predictor for poor prognosis in endometrial carcinoma. Hum Pathol 36:1281–1288
Lee EC, Frolov A, Li R, Ayala G, Greenberg NM (2001) Targeting Aurora kinases for the treatment of prostate cancer. Cancer Res 66:4996–5002
Li JJ, Li SA (2006) Mitotic kinases: the key to duplication, segregation, and cytokinesis errors, chromosomal instability, and oncogenesis. Pharmacol Ther 111:974–984
Lo Muzio L, Pannone G, Leonardi R, Staibano S, Mignogna MD, De Rosa G, Kudo Y, Takata T, Altieri DC (2003) Survivin, a potential early predictor of tumor progression in the oral mucosa. J Dent Res 82:923–928
Lo Muzio L, Pannone G, Staibano S, Mignogna MD, Rubini C, Mariggio MA, Procaccini M, Ferrari F, De Rosa G, Altieri DC (2003) Survivin expression in oral squamous cell carcinoma. Br J Cancer 89:2244–2248
Minoshima Y, Kawashima T, Hirose K, Tonozuka Y, Kawajiri A, Bao YC, Deng X, Tatsuka M, Narumiya S, May WS Jr, Nosaka T, Semba K, Inoue T, Satoh T, Inagaki M, Kitamura T (2003) Phosphorylation by aurora B converts MgcRacGAP to a RhoGAP during cytokinesis. Dev Cell 4:549–560
Murata-Hori M, Wang YL (2002) The kinase activity of aurora B is required for kinetochore microtubule interactions during mitosis. Curr Biol 12:894–899
Nikiforov YE (2005) Editorial: anaplastic carcinoma of the thyroid—will aurora B light a path for treatment? J Clin Endocrinol Metab 90:1243–1245
Ota T, Suto S, Katayama H, Han ZB, Suzuki F, Maeda M, Tanino M, Terada Y, Tatsuka M (2002) Increased mitotic phosphorylation of histone H3 attributable to AIM-1/Aurora B overexpression contributes to chromosome number instability. Cancer Res 62:5168–5177
Sorrentino R, Libertini S, Pallante PL, Troncone G, Palombini L, Bavetsias V, Spalletti-Cernia D, Laccetti P, Linardopoulos S, Chieffi P, Fusco A, Portella G (2005) Aurora B over expression associates with the thyroid carcinoma undifferentiated phenotype and is required for thyroid carcinoma cell proliferation. J Clin Endocrinol Metab 90:928–935
Tatsuka M, Katayama H, Ota T, Tanaka T, Odashima S, Suzuki F, Terada Y (1998) Multinuclearity and increased ploidy caused by overexpression of the aurora B and Ipl1-like midbody-associated protein mitotic kinase in human cancer cells. Cancer Res 58:4811–4816
Temme A, Rieber EP, Schmitz M, Moreqenroth A, Weiqie B, Rieqer MA, Kiessling A, Rieber EP (2005) Increased p21(ras) activity in human fibroblasts transduced with survivin enhances cell proliferation. Biochem Biophys Res Commun 327:765–773
Terada Y (2001) Role of chromosomal passenger complex in chromosome segregation and cytokinesis. Cell Struct Funct 26:653–657
Terada Y, Tatsuka M, Suzuki F, Yasuda Y, Fujita S, Otsu M (1998) AIM-1: a mammalian midbody-associated protein required for cytokinesis. EMBO J 17:667–676
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Qi, G., Ogawa, I., Kudo, Y. et al. Aurora-B expression and its correlation with cell proliferation and metastasis in oral cancer. Virchows Arch 450, 297–302 (2007). https://doi.org/10.1007/s00428-006-0360-9
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DOI: https://doi.org/10.1007/s00428-006-0360-9