Journal
JOURNAL OF ONCOLOGY
Volume 2010, Issue -, Pages -Publisher
HINDAWI LTD
DOI: 10.1155/2010/530130
Keywords
-
Categories
Funding
- Canadian Institutes for Health Research
- Fonds de la Recherche en Sante du Quebec (FRSQ- Reseau du Cancer)
Ask authors/readers for more resources
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 G(0)-G(1) cell cycle arrest and reduction of S and G(2)-M phase using 2 and 5 mu Mconcentrations 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 beta-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 beta-catenin alteration, suggesting that Src inhibitor, in comparison to EGF-R, is a promising therapeutic agent for human cervical cancer.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available