The Effect of Aurora Kinase Inhibitor on Adhesion and Migration in Human Breast Cancer Cells and Clinical Implications

Huishan Zhao, Sioned Owen, Eleri L. Davies, Wen G. Jiang, Tracey A. Martin

Abstract


Background: The Aurora kinase family is comprised of highly conserved serine/threonine protein kinases that are known to be crucial in the regulation of the cell cycle. Aberrant expression of Aurora kinases has been demonstrated in certain malignancies. We aimed to examine the expression of Aurora kinases in human breast cancer tissues and to investigate the cellular impact of Aurora kinases inhibitor on breast cancer cells.

Methods: The expression of Aurora kinase A/B/C was individually examined in tumor specimens (n = 106) and normal tissues (n = 29) from breast cancer patients using quantitative real-time PCR (Q-PCR) and immunohistochemistry. Cells were treated with the corresponding inhibitor, and then migration and adhesion were evaluated by electric cell impedance sensing assay. The proliferation of breast cancer cells treated with the inhibitor was examined using in vitro models.

Results: High levels of Aurora kinase B and C were found in the tumor tissues from breast cancer patients, but low levels of Aurora kinase A were seen in normal tissues at the mRNA level and immunohistochemistry. The mRNA expression level of Aurora kinase B and C had a negative correlation with grade staging, staging and survival rate in breast cancer patients, whilst Aurora kinase A exhibited a converse expression. The inhibitor ZM447439 promoted adhesion of the human breast cancer cell line MDA-MB-231 and inhibited the migration of MCF-7 human breast cancer cells.

Conclusion: Taken together, the expression of Aurora kinase B and C was down-regulated in breast tumor tissues but Aurora kinase A was not. Aurora kinase may have a key role in the progression and metastasis of breast cancer.




World J Oncol. 2017;8(5):151-161
doi: https://doi.org/10.14740/wjon1062w

 


Keywords


Breast cancer; Metastasis; Aurora kinases A, B and C; Immunohistochemistry; Migration; Adhesion; Proliferation; ZM447439

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