World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access
Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc
Journal website http://www.wjon.org

Original Article

Volume 8, Number 5, October 2017, pages 151-161


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

Figures

Figure 1.
Figure 1. Expression of Aurora kinase A in breast cancer tissues. (a) Aurora kinase A transcripts level was decreased in human breast cancer. (b) Immunohistochemical staining of Aurora kinase A in normal breast tissue (left panel) and tumor tissue (right panel).
Figure 2.
Figure 2. Expression of Aurora kinase B and C in breast cancer tissues. (a) The expression of Aurora kinase B is higher in breast cancer tissues. (b) Immunohistochemical staining of Aurora kinase B in normal background tissue (left panel) and breast tumor tissue (right panel). (c) Aurora kinase C transcripts level was increased in human breast cancer.
Figure 3.
Figure 3. Correlation of Aurora kinase A expression with Nottingham prognostic index (NPI), grade, TNM staging and prognosis. (a) Lowest level of Aurora kinase A was observed in patients with poor prognostic index among these three groups (**P < 0.01 NPI-3 vs. NPI-1). (b) Node negative tumors had higher levels of Aurora kinase A transcript than node positive tumor. (c) Levels of expression of Aurora kinase A in breast tumor tissues in connection with grade and (d) with TNM status (*P < 0.05 grade 3 vs. grade 1; *P < 0.05 TNM 2 vs. TNM 1). (e) Levels of Aurora kinase A transcript and clinical outcomes. Aurora kinase A expression progressively decreased in the patients with metastasis disease, with local recurrence and die of breast cancer, compared with patient with disease free (*P < 0.05 metastasis vs. disease free; **P < 0.01 local recurrence vs. disease free). (f) Lower level of Aurora kinase A expression in patients with poor prognosis.
Figure 4.
Figure 4. Correlation of Aurora kinase B and C expression with Nottingham prognostic index (NPI), grade staging and prognosis. Top panel (Aurora kinase B): (a) Highest level of Aurora kinase B in patients with poor prognostic index among these three groups. (b): Grade 3 tumor had higher level of Aurora kinase B transcript than grade 1 and 2. (c) Levels of Aurora kinase B transcript and clinical outcomes. Aurora kinase B expression progressively increased in the patients with local recurrence and die of breast cancer, compared with patient with disease free. (d) Higher level of Aurora kinase B expression in patients with poor prognosis. Bottom panel (Aurora kinase C): (e) Higher level of Aurora kinase C in patients with poor prognostic index than with moderate and poor prognosis. (f) A stepwise increase of levels of Aurora kinase C was found from grade 1 to grade 3 staging. (g) Lever of Aurora kinase C expression was higher in the patients with local recurrence than with metastasis disease and disease free. (h) Lower level of Aurora kinase C expression in patients with good prognosis.
Figure 5.
Figure 5. Effects of Aurora kinases inhibitor on the adhesion of breast cancer cells. Top panel: The response of MCF-7 to ZM447439. (a) Migration traces of MCF-7 cell’s response to ZM447439 at different concentrations. (b) 3D image of MCF-7 (control); (c and d) Response of MCF-7 to ZM447439 at 50 and 500 nM, respectively. Bottom panel: The response of MDA-MB-231 to ZM447439. (e) Traces of MDA-MB-231 cell’s response to ZM447439 at different concentrations. (f) 3D image of MDA-MB-231 (control); (g and h) Response of MDA-MB-231 to ZM447439 at 50 and 500 nM, respectively.

Tables

Table 1. Breast Cancer Patient Clinical Data Details
 
Clinical dataSample no.
Tissue sample
  Normal34
  Tumor118
NPI
  163
  236
  315
Tumor grade
  121
  241
  37
TNM staging
  I2
  II36
  III7
  IV4
Survival status
  184
  26
  35
  416

 

Table 2. Primers Sequences (Q-PCR)
 
MolecularSense primers (5′-3′)Antisense primers (5′-3′)
Aurora kinase AGGTCAGTACATGCTCCATCTACTGAACCTGACCGTACACAGAGATCCACCTTCTCATC
Aurora kinase BGCAGAGAGATCGAAATCCAACTGAACCTGACCGTACAGGGGCATACTCTAGGAATCAA
Aurora kinase CTGGAGTGCTCTGCTATGAGACTGAACCTGACCGTACCGTACAGCATTGATAGTGGAAACCTC
GAPDH (Q-PCR)CTGAGTACGTCGTGGAGTCACTGAACCTGACCGTACAGAGATGATGACCCTTTTG