Yanchun Meng1, Qunfang Xu2, Lin Chen3, Lingfei Wang4, Xichun Hu5. 1. Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Phase I Clinical Trial Center, Shanghai Cancer Center, Fudan University, Shanghai, China. 2. Clinical Laboratory, Capital Medical University Electric Teaching Hospital (State Grid Coporation of China Beijing Electric Power Hospital), Beijing, China. 3. Department of Colorectal Surgery, Department of General Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. 4. Department of Oncology, the 903rd Hospital of PLA, Hangzhou, 310013, China. Electronic address: bsocnur@yeah.net. 5. Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Phase I Clinical Trial Center, Shanghai Cancer Center, Fudan University, Shanghai, China. Electronic address: xichunhufudan@126.com.
Abstract
OBJECTIVE: The purpose of this study was to explore the functional roles of SOX2 in the progression of breast cancer and relevant molecular mechanism. METHODS: A total of 108 breast cancer patients were included, and breast cancer cell line MDA-MB-231 was selected for this research. Real time-qualitative polymerase chain reaction (RT-qPCR) was conducted to measure the expression level of SOX2 mRNA. MTT and Transwell assays were used to detected the proliferation, migration and invasion of breast cancer cells, respectively. Luciferase reporter assay was conducted to reveal the relationship of SOX2 with PTEN. Western blot was performed to detect the expressions of Wnt/β-catenin pathway-related proteins. RESULTS: The expression of SOX2 mRNA was up-regulated in breast cancer tissues and cells (P < 0.001). SOX2 expression was significantly associated with TNM stage and lymph node metastasis of breast cancer patients (P < 0.05). SOX2 knockdown significantly inhibited the proliferation, migration and invasion of breast cancer cells (P < 0.05). PTEN was a direct target of SOX2. The inhibition of PTEN could significantly suppress the progression of breast cancer cells with SOX2 overexpression. SOX2 knockdown also inhibited the expressions of β-catenin, TCP-4, FZD7, C-myc and MMP-7 proteins. Moreover, PTEN knockdown reversed the results caused by SOX2 overexpression, that is, increased expressions of β-catenin, TCP-4, FZD7, C-myc and MMP-7 proteins (P < 0.05). CONCLUSION: SOX2 promotes the progression of breast cancer through activating Wnt/β-catenin signaling pathway via regulating PTEN.
OBJECTIVE: The purpose of this study was to explore the functional roles of SOX2 in the progression of breast cancer and relevant molecular mechanism. METHODS: A total of 108 breast cancerpatients were included, and breast cancer cell line MDA-MB-231 was selected for this research. Real time-qualitative polymerase chain reaction (RT-qPCR) was conducted to measure the expression level of SOX2 mRNA. MTT and Transwell assays were used to detected the proliferation, migration and invasion of breast cancer cells, respectively. Luciferase reporter assay was conducted to reveal the relationship of SOX2 with PTEN. Western blot was performed to detect the expressions of Wnt/β-catenin pathway-related proteins. RESULTS: The expression of SOX2 mRNA was up-regulated in breast cancer tissues and cells (P < 0.001). SOX2 expression was significantly associated with TNM stage and lymph node metastasis of breast cancerpatients (P < 0.05). SOX2 knockdown significantly inhibited the proliferation, migration and invasion of breast cancer cells (P < 0.05). PTEN was a direct target of SOX2. The inhibition of PTEN could significantly suppress the progression of breast cancer cells with SOX2 overexpression. SOX2 knockdown also inhibited the expressions of β-catenin, TCP-4, FZD7, C-myc and MMP-7 proteins. Moreover, PTEN knockdown reversed the results caused by SOX2 overexpression, that is, increased expressions of β-catenin, TCP-4, FZD7, C-myc and MMP-7 proteins (P < 0.05). CONCLUSION:SOX2 promotes the progression of breast cancer through activating Wnt/β-catenin signaling pathway via regulating PTEN.