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Journal of Oncology
Volume 2010, Article ID 530130, 10 pages
http://dx.doi.org/10.1155/2010/530130
Research Article

Locking Src/Abl Tyrosine Kinase Activities Regulate Cell Differentiation and Invasion of Human Cervical Cancer Cells Expressing E6/E7 Oncoproteins of High-Risk HPV

1Segal Cancer Centre, Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis-Jewish General Hospital, Davis-Jewish General Hospital, McGill University, 3755, Ch. de la Cote Ste-Catherine, Montreal, QC, Canada H3T 1E2
2Faculty of Pharmacy, University of Aleppo, Aleppo, Syria
3Syrian Research Cancer Center of the Syrian Society against Cancer, Aleppo, Syria
4Department of Clinical Medicine and Prevention, University of Milano-Bicocca, 20052 Monza, Italy
5Department of Mechanical Engineering, Concordia University, Montreal, QC, Canada H4B 1R2
6Department of Oncology, Faculty of Medicine, McGill University, QC, H3G1M8, Canada

Received 2 March 2010; Revised 16 June 2010; Accepted 6 July 2010

Academic Editor: Therese Deramaudt

Copyright © 2010 Amber Yasmeen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

In this study, we compared the effects of SKI-606 with Iressa, Src/Abl and EGF-R kinase inhibitors, respectively, on selected parameters in HeLa and SiHa cervical cancer cell lines, which express E6/E7 oncoproteins of high-risk HPV types 18 and 16, respectively. Our results show that SKI-606 and Iressa inhibit cell proliferation and provoke - cell cycle arrest and reduction of S and -M phase using 2 and 5  concentrations of these inhibitors. In contrast, SKI-606 induces differentiation to an epithelial phenotype “mesenchymal-epithelial transition”; thus SKI-606 causes a dramatic decrease in cell motility and invasion abilities of HeLa and SiHa cancer cells, in comparison to untreated cells and Iressa-treated cells in which these parameters are only slightly affected. These changes are accompanied by a regulation of the expression patterns of E-cadherin and catenins. The molecular pathway analysis of Src/Abl inhibitor revealed that SKI-606 blocks the phosphorylation of -catenin and consequently converts its role from a transcriptional regulator to a cell-cell adhesion molecule. Our findings indicate that SKI-606 inhibits signaling pathways involved in regulating tumor cell migration and invasion genes via -catenin alteration, suggesting that Src inhibitor, in comparison to EGF-R, is a promising therapeutic agent for human cervical cancer.