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E-cadherin decreased human breast cancer cells sensitivity to staurosporine by up-regulating Bcl-2 expression
Authors:Wang Liying  Li Zengxia  Wang Can  Yang Yong  Sun Lidong  Yao Wantong  Cai Xiumei  Wu Guoqiang  Zhou Feng  Zha Xiliang
Institution:a Key Laboratory of Glycoconjugate Research, Ministry of Health, Shanghai 200032, China
b Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Abstract:E-cadherin, a well-characterized cell-cell adhesion molecule, executes multifunction roles on cell behaviors. However, its effect on chemo-resistance remains controversial. In this study, we found that E-cadherin positive breast cell lines were less sensitive to staurosporine compared to E-cadherin negative ones. Next, we substantiated that the expression of E-cadherin in MDA-MB-435 cells could partly counteract the cytotoxic effect induced by staurosporine through a series of apoptosis assay. The resistance of E-cadherin over-expressing cells to staurosporine may due to the up-regulation of Bcl-2/Bax ratio. When E-cadherin interference plasmids were transfected into MCF-7 cells, Bcl-2 expression was down-regulated. Moreover, perturbation of E-cadherin function by blocking the cell-cell contact resulted in decreased cellular levels of Bcl-2 protein expression. All these results demonstrated the chemo-resistance function of E-cadherin in the condition of staurosporine treatment, therefore, might contribute effective therapeutic strategies in breast carcinoma.
Keywords:E-cadherin  Staurosporine  Bcl-2  Apoptosis  Breast cancer
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