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 μM 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 β-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 β-catenin alteration, suggesting that Src inhibitor, in comparison to EGF-R, is a promising therapeutic agent for human cervical cancer.

Yasmeen, A., Alachkar, A., Dekhil, H., GAMBACORTI PASSERINI, C., Al Moustafa, A. (2010). Locking Src/Abl tyrosine kinase activities regulate cell differentiation and invasion of human cervical cancer cells expressing E6/E7 oncoproteins of high-risk HPV. JOURNAL OF ONCOLOGY, 2010 [10.1155/2010/530130].

Locking Src/Abl tyrosine kinase activities regulate cell differentiation and invasion of human cervical cancer cells expressing E6/E7 oncoproteins of high-risk HPV

GAMBACORTI PASSERINI, CARLO;
2010

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 G(0)-G(1) cell cycle arrest and reduction of S and G(2)-M phase using 2 and 5 μM 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 β-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 β-catenin alteration, suggesting that Src inhibitor, in comparison to EGF-R, is a promising therapeutic agent for human cervical cancer.
Articolo in rivista - Articolo scientifico
Tyrosine Kinase, Src/Abl
English
2010
2010
530130
none
Yasmeen, A., Alachkar, A., Dekhil, H., GAMBACORTI PASSERINI, C., Al Moustafa, A. (2010). Locking Src/Abl tyrosine kinase activities regulate cell differentiation and invasion of human cervical cancer cells expressing E6/E7 oncoproteins of high-risk HPV. JOURNAL OF ONCOLOGY, 2010 [10.1155/2010/530130].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/33155
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