The Mechanism Of CXCL12/CXCR4Signaling In Tamoxifen Resistant Breast Cancer Cells

Objective:Observing the crosstalk between CXCL12/CXCR4and EGFR/Her2signalings in tamoxifen resistant breast cancer cells. Illustrating the mechanism oftamoxifen resistance in hormone dependent breast cancer cells.Method: Inducing a tamoxifen-resistant phenotype (MCF-7/TAM-R) of the humanbreast cancer cell line MCF-7by culture for6months treatment with4-hydroxytamoxifen (TAM),then test the stability of the cell. Detecting the expression of CXCR4、Src,HER2,EGFR by Western blotting.MCF-7and MCF-7/TAM-R cells were treated withCXCL12,AMD3100,a CXCR4inhibitor,PP2,a Src kinase inhibitor. Then observing theeffect between CXCR4,HER2and Src.Cell viability was observed by MTT assay. Thetotal and phosphorylated expression of HER2,Src were evaluated by Western blottingand analyzed the gradation value and relative magnitude with image analysis software.Result: A stable, tamoxifen-resistant subline had established. Comparing withMCF-7, MCF-7/TAM-R cell expressed a high level of CXCR4,Src,HER2. InMCF-7/TAM-R cell, HER2,Src and cell growth could be stimulated by CXCR4, andthrough Src kinase activation, HER2could be stimulated by CXCL12/CXCR4singaling,which could be inhibited by AMD3100or PP2.Conclusion: In MCF-7/TAM-R cell, HER2and cell growth could be stimulated byCXCL12/CXCR4singaling through Src kinase activation,which played an importantrole in tamoxifen resistance.