Expression of budding uninhibited by benzimidazoles - 1 and mitotic arrest deficient - 2 in endometrial carcinoma and its significance

Objective: The aim of this study was to explore the expression of budding uninhibited by benzimidazoles-1 (Bub1) and mitotic arrest deficient- 2 (Mad2) in endometrial carcinoma and its significance. Materials and Methods: The expression of Bub1 and Mad2 in 30 human normal endometrial tissues (group A), 30 complexly-hyperplastic endometrial tissues (group B), and 63 endometrial carcinoma tissues (group C) was observed using immunohistochemistry (the streptavidin-peroxidase method). Results: The positive expression rates of Bub1 in groups A, B, and C were 86.67%, 56.67%, and 28.57%, respectively. The positive rate of Bub1 protein was correlated with the differentiation degree and clinical stage of endometrial carcinoma (p < 0.05) other than lymph node metastasis (p > 0.05): A higher differentiation degree and a more advanced stage of endometrial carcinoma indicated a higher positive rate of Bub1 protein. The positive rates of Mad2 protein in groups A, B, and C were 23.33%, 56.67%, and 85.71%, respectively. The positive rate of Mad2 protein was correlated with the differentiation degree of endometrial carcinoma (p < 0.05) other than its clinical stage and lymph node metastasis (p > 0.05): A lower differentiation degree indicated a higher positive rate of Mad2 protein. Bub1 and Mad2 proteins were negatively correlated in the endometrial carcinoma tissues (r = - 0.719, p < 0.001). Conclusion: Bub1 and Mad2 proteins interact with each other. They may play an important role in the initiation and development of endometrial carcinoma.

Endometrial carcinoma; Budding uninhibited by benzimidazoles-1 (Bub1); Mitotic arrest deficient 2-like protein 1; Spindle checkpoint.

[1] Hannisdal K., Burum- Auensen E., Schjølberg A., De Angelis P.M., Clausen O.P.: “Correlation between reduced expression of the spindle checkpoint protein BubR1 and bad prognosis in tonsillar carcinomas”. Head Neck, 2010, 32, 1354.

[2] Kato T., Daigo Y., Aragaki M., Ishikawa K., Sato M., Kondo S. et al.: “Overexpression of MAD2 predicts clinical outcome in primary lung cancer patients”. Lung Cancer, 2011, 74, 124.

[3] Li Z.Q., Zhang J.B.: “Cell Cycle and Regulation”. Oncology Progress, 2004, 2, 146.

[4] Kadhiin M.A., Macdonald D.A., Goodhead D.T., Lorimore S.A., Maarsden S.J., Wright E.G.: “Transition of chromosome instability after plutonium-particle irradiation”. Nature, 1992, 355, 738.

[5] Luo M., Weng Y., Tang J., Hu M., Liu Q., Jiang F. et al.: “Mi-croRNA-450a-3p Represses Cell Proliferation and Regulates Embryo Development by Regulating Bub1 Expression in Mouse”. PLoS One, 2012, 7, e47914.

[6] Sun S.C., Kim N.H.: “Spindle assembly checkpoint and its regulators in meiosis”. Hum. Reprod. Update, 2012, 18, 60.

[7] Marchetti F., Venkatachalam S.: “The multiple roles of Bub1 in chromosome segregation during mitosis and meiosis”. Cell Cycle, 2010, 9, 58.

[8] Jeganathan K., Malureanu L., Baker D.J., Abraham S.C., van Deursen J.M.: “Bub1 mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis”. J. Cell Biol., 2007, 179, 255.

[9] Gao F., Ponte J.F., Papageorgis P., Levy M., Ozturk S., Lambert A.W. et al.: “hBub1 deficiency triggers a novel p53 mediated early apoptotic checkpoint pathway in mitotic spindle damaged cells”. Cancer Biol. Ther., 2009, 8, 627.

[10] Ma Z., Liu L.: “The significance of DNA ploidy and S-phrase fraction (SPF) in endometrial carci. Journal of Maternity and Child Care of China, 2006, 21, 3173.

[11] Duesberg P.: “Genetic instability of cancer cells is proportional to their degree of aneuploidy”. P. Natl. Acad. Sci. U. S. A., 1998, 95, 13692.

[12] Ricke R.M., Jeganathan K.B., van Deursen J.M.: “Bub1 overexpression induces aneuploidy and tumor formation through Aurora B kinase hyperactivation”. J. Cell Biol., 2011, 193, 1049.

[13] Pennisi E.: “Cell division gatekeepers identified”. Science, 1998, 279, 477.

[14] Orr B., Bousbaa H., Sunkel C.E.: “Mad2-independent spindle assembly checkpoint activation and controlled metaphase-anaphase transition in Drosophila S2 cells”. Mol. Biol. Cell, 2007, 18, 850.

[15] Michel L.S., Liberal V.: “Mad2 haplo-insuffciency causes premature anaphase and chromosome instability in mammalian cell”. Nature, 2001, 409, 355.

[16] Sotillo R., Hernando E., Díaz-Rodríguez E., Teruya-Feldstein J., Cordón-Cardo C., Lowe S.W. et al.: “Mad2 overexpression promotes aneuploidy and tumorigenesis in mice”. Cancer Cell, 2007, 11, 9.

[17] Ge S., Skaar JR., Pagano M.: “APC/C- and Mad2-mediated degradation of Cdc20 during spindle checkpoint activation”. Cell Cycle, 2009, 8, 167.

[18] Saitoh S., Kobayashi Y., Ogiyama Y., Takahashi K.: “Dual regulation of Mad2 localization on kinetochores by Bub1 and Dam1/DASH that ensure proper spindle interaction”. Mol. Biol. Cell, 2008, 19, 3885.

[19] Tipton A.R., Tipton M., Yen T., Liu S.T.: “Closed MAD2 (C-MAD2) is selectively incorporated into the mitotic checkpoint complex (MCC)”. Cell Cycle, 2011, 10, 3740.

[20] Brevini T.A., Pennarossa G., Maffei S., Tettamanti G., Vanelli A., Isaac S. et al.: “Centrosome amplification and chromosomal instability in human and animal parthenogenetic cell lines”. Stem. Cell Rev., 2012, 8, 1076.