TGF-β1在乳腺癌EMT中作用机制探讨
发布时间：2018-08-11 10:35
【摘要】：目的乳腺癌的发病率不断上升,上皮-间质转化(epithelial to mesenchymal transition,EMT)在乳腺癌病变中广泛存在。本研究探讨TGF-β1在乳腺癌EMT中的作用及PTPN12在此过程中的作用和相关机制。方法蛋白质印迹法检测TGF-β1处理乳腺癌细胞后EMT相关基因以及PI3K、p-AKT和mTOR的表达;免疫组织化学检测乳腺癌组织和癌旁组织中PTPN12表达;免疫共沉淀检测PTPN12和p-AKT是否有直接相互作用;蛋白质印迹法检测转染LV5-PTPN12后,E-Cadherin、Vimentin、Fibronectin、PI3K、p-AKT和mTOR蛋白的表达情况;裸鼠皮下成瘤检测PTPN12对乳腺癌成瘤大小以及体积的影响。结果 NC组和TGF-β1组Vimentin蛋白表达量分别为(17.2±2.3)%和(79.7±8.3)%,t=12.5,P=0.008;Fibronectin蛋白表达量分别(17.4±2.3)%和(77.4±7.5)%,t=12.1,P=0.016。PTPN12在乳腺癌组织中表达明显降低,PTPN12与乳腺癌病理分期分级以及腋窝淋巴结受累数目有关,NC组和TGF-β1组PI3K蛋白表达量分别为(18.6±1.9)%和(76.3±5.9)%,t=12.1,P=0.029;p-AKT蛋白表达量分别为(27.6±3.2)%和(54.1±6.2)%,t=11.7,P=0.013;mTOR蛋白表达量分别为(35.2±3.2)%和(72.2±5.3)%,t=18.3,P=0.031;PTPN12和p-AKT有直接相互作用;PTPN12可以抑制TGF-β1诱导的EMT,LV5-PTPN12组和LV5-NC组Vimentin蛋白表达量分别为(17.2±2.3)%和(79.7±8.3)%,t=11.9,P0.018;Fibronectin蛋白表达量分别为(17.4±2.3)%和(77.4±7.5)%,t=10.2,P=0.019;E-Cadherin蛋白表达量分别为(82.1±8.4)%和(0.22±0.02)%,t=13.7,P0.001。PTPN12可以通过PI3K/AKT信号通路起作用,LV5-PTPN12组和LV5-NC组PI3K蛋白表达量分别为(13.2±1.2)%和(56.2±5.1)%,t=7.1,P=0.021;p-AKT蛋白表达量分别为(23.5±2.5)%和(77.1±6.3)%,t=9.2,P=0.008;mTOR蛋白表达量分别为(28.2±3.1)%和(71.7±6.1)%,t=12.8,P=0.032。体内实验表明,与对照组相比,LV5-PTPN12组荷瘤小鼠肿瘤体积和体质量都明显变小,LV5-PTPN12组和LV5-NC组肿瘤体积分别为(2.8±0.2)和(0.4±0.02)cm~3,t’=13.8,P0.001;体质量分别为(3.1±0.3)和(0.4±0.02)g,t’=18.6,P0.001。结论 PTPN12在TGF-β1作用下通过PI3K/AKT信号通路诱导乳腺癌的EMT中起抑制作用。
[Abstract]:Objective the incidence of breast cancer is increasing and epithelial-interstitial transformation (epithelial to mesenchymal) is widely used in breast cancer. The purpose of this study was to investigate the role of TGF- 尾 1 in EMT of breast cancer and the role and mechanism of PTPN12 in this process. Methods the expression of EMT related genes, PI3KPP-AKT and mTOR in breast cancer cells treated with TGF- 尾 1 was detected by Western blot, PTPN12 expression in breast cancer tissues and adjacent tissues was detected by immunohistochemistry, and whether there was direct interaction between PTPN12 and p-AKT was detected by immunoprecipitation. The expression of PI3KTp-AKT and mTOR protein in LV5-PTPN12 was detected by Western blot, and the effect of PTPN12 on the size and volume of breast cancer was detected by subcutaneous tumorigenesis in nude mice. Results the expression of Vimentin protein in NC group and TGF- 尾 1 group were (17.2 卤2.3)% and (79.7 卤8.3)%, respectively. The expression of Vimentin protein was (17.4 卤2.3)% and (77.4 卤7.5)%, respectively. TGF-尾1缁凱I3K铔嬬櫧琛ㄨ揪閲忓垎鍒负(18.6卤1.9)%鍜，
本文编号：2176752
[Abstract]:Objective the incidence of breast cancer is increasing and epithelial-interstitial transformation (epithelial to mesenchymal) is widely used in breast cancer. The purpose of this study was to investigate the role of TGF- 尾 1 in EMT of breast cancer and the role and mechanism of PTPN12 in this process. Methods the expression of EMT related genes, PI3KPP-AKT and mTOR in breast cancer cells treated with TGF- 尾 1 was detected by Western blot, PTPN12 expression in breast cancer tissues and adjacent tissues was detected by immunohistochemistry, and whether there was direct interaction between PTPN12 and p-AKT was detected by immunoprecipitation. The expression of PI3KTp-AKT and mTOR protein in LV5-PTPN12 was detected by Western blot, and the effect of PTPN12 on the size and volume of breast cancer was detected by subcutaneous tumorigenesis in nude mice. Results the expression of Vimentin protein in NC group and TGF- 尾 1 group were (17.2 卤2.3)% and (79.7 卤8.3)%, respectively. The expression of Vimentin protein was (17.4 卤2.3)% and (77.4 卤7.5)%, respectively. TGF-尾1缁凱I3K铔嬬櫧琛ㄨ揪閲忓垎鍒负(18.6卤1.9)%鍜，
本文编号：2176752
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