The Effect Of Wnt7b On Breast Cancer Cell Growth,Migration And Invasion

Objective: Wnt/?-catenin pathway regulates cell proliferation,apoptosis and motility,and angiogenesis through downstream molecules such as cyclin D1,c-Myc,MMP-7,VEGF.Aberrant activation of this pathway can cause uncontrolled cell growth and increased cell motility due to overexpression of these downstream molecules.Therefore,Wnt/?-catenin plays an important role in a series of human tumors.In the present study,we intend to determine Wnt7 b expression,evaluate Wnt7b/?-catenin signaling activation,and analyze the effect of Wnt7 b on breast cancer cell proliferation,apoptosis,migration and invasion.Methods: 44 human breast cancer tissues,10 adjacent non-tumor tissues,human breast cancer cell MDA-MB-231,BT-549,T47 D,MCF-7 and mouse breast cancer cell 4T1 were included in the present study.Expression of Wnt7 b and ?-catenin in tissues was examined by immunohistochemical staining(IHC).Expression of Wnt7 b and ?-catenin in breast cancer cells was detected by Western blot and immunofluorescence.Wnt7 b si RNA transfection was performed to downregulate Wnt7 b expression.Cell viability was assessed by MTT.Cell proliferation and apoptosis was analyzed by flow cytometry.Cell migration and invasion was analyzed by transwell.Expression of Cyclin D1,c-Myc,MMP-7,VEGF,E-cadherin and Vimentin was detected by Western blot.Results: Wnt7 b expression in breast cancer tissues is significantly higher than that in adjacent non-tumor samples.Wnt7 b was expressed in all breast cancer cells.Wnt7 b and ?-catenin were both expressed in parts of breast cancer tissues,while in some other breast cancer tissues which expressed Wnt7 b,?-catenin expression was hardly detected.Wnt7 b si RNA transfection downregulated Wnt7 b expression in MDA-MB-231 and MCF-7 cells,but only reduced ?-catenin expression in MDA-MB-231 cell.Wnt7 b knockdown decreased MDA-MB-231 cell viability,migration and invasion,and increased MDA-MB-231 cell apoptosis,while had no effect on MCF-7 cell apoptosis,migration and invasion.Wnt7 b knockdown in MDA-MB-231 cell decreased c-Myc,MMP-7 and VEGF expression,but had no effect on Cyclin D1,E-cadherin and Vimentin expression.Conclusion: Wnt7 b is overexpressed in breast cancers.Wnt7 b regulates growth,migration and invasion of certain breast cancer cell,suggesting Wnt7 b can promote growth and metastasis of some breast cancers.Wnt7 b may exert its effect on breast cancer cell through ?-catenin pathway activation.