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δ-catenin通过PI3K/AKT信号通路促进乳腺癌细胞上皮间质转化的机制研究 被引量:2

The mechanism research of δ-catenin promoting epithelial mesenchymal transition of breast cancer cells through PI3K/AKT signaling pathway
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摘要 目的探讨δ-catenin通过PI3K/AKT信号通路促进乳腺癌细胞上皮间质转化(epithelial-mesenchymal transition,EMT)的作用机制,为乳腺癌的靶向治疗提供科学依据。方法选取人乳腺癌细胞系MDA-MB-231,对细胞进行不同处理后分为3组,分别为过表达组(δ-catenin)、LY294002组(δ-catenin+LY)和对照组,δ-catenin组处理方法为δ-catenin表达质粒转染入乳腺癌细胞系,δ-catenin+LY组为LY294002和δ-catenin表达质粒与乳腺癌细胞系共同孵育48 h,对照组为空白质粒转染入乳腺癌细胞系。应用Western blotting方法、PI3K/AKT通路抑制剂LY294002和侵袭实验后,分别比较δ-catenin组、δ-catenin+LY组与对照组的EMT(上皮性标记E-cadherin指标、间叶性标记N-cadherin和Vimentin指标)、信号通路蛋白(AKT、p-AKT)、内参照β-actin蛋白以及肿瘤侵袭能力(穿过微孔膜的肿瘤细胞数量等)的差异。结果δ-catenin组上皮性标记E-cadherin与对照组相比明显减少[(0.62±0.04)比(1.09±0.08)],间叶性标记N-cadherin、Vimentin和p-AKT表达水平明显增加[(1.52±0.08)比(0.51±0.04),(1.02±0.07)比(0.27±0.06),(1.43±0.07)比(0.69±0.11),P<0.05]。δ-catenin组穿过微孔膜的肿瘤细胞数量显著高于对照组[(39.18±4.28)比(9.32±1.36),P<0.05]。δ-catenin+LY组p-AKT表达水平与对照组相比明显减少[(0.21±0.03)比(0.49±0.08),P<0.05];δ-catenin+LY组与对照组在E-cadherin、N-cadherin、Vimentin的表达水平和穿过微孔膜的肿瘤细胞数量比较,差异均无统计学意义(P>0.05)。结论δ-catenin可能通过激活PI3K/AKT通路而促进乳腺癌细胞的EMT和侵袭能力的增强。 Objective To explore the mechanism ofδ-catenin promoting epithelial-mesenchymal transition(EMT)of breast cancer cells through PI3K/AKT signaling pathway,and provide scientific basis for targeted therapy of breast cancer.Methods The human breast cancer cell line MDA-MB-231 were selected,after different treatment,the cells were divided into three groups,namely the over-expression group(δ-catenin),LY294002 group(δ-catenin+LY)and control group(control).Theδ-catenin group was transfected into breast cancer cell lines withδ-catenin expression plasmid,theδ-catenin+LY group was co-incubated with breast cancer cell lines with LY294002 andδ-catenin expression plasmid for 48 h,while the control group was transfected into breast cancer cell lines with blank plasmid.Western blotting,PI3K/AKT pathway inhibitor LY294002 and invasion experiment were used to compare EMT(epithelial marker E-cadherin index,mesenchymal marker Ncadherin and Vimentin),signal pathway proteins(AKT,p-AKT),internal referenceβand tumor invasion ability amongδ-catenin group,δ-catenin+LY group and control group,respectively.Results Compared with the control group,the epithelial marker E-cadherin inδ-catenin group decreased significantly[(0.62±0.04)vs.(1.09±0.08)],and the expression levels of mesenchymal markers N-cadherin,Vimentin and p-AKT increased significantly[(1.52±0.08)vs.(0.51±0.04),(1.02±0.07)vs.(0.27±0.06),(1.43±0.07)vs.(0.69±0.11)],the differences were statistically significant(all P<0.05).The number of tumor cells passing through the microporous membrane in theδ-catenin group was significantly higher than that in the control group[(39.18±4.28)vs.(9.32±1.36)],and the difference was statistically significant(P<0.05).Compared with control group,the expression level of p-AKT inδ-catenin+LY group decreased significantly[(0.21±0.03)vs.(0.49±0.08),P<0.05].The differences of expression levels of E-cadherin,N-cadherin and Vimentin and the number of tumor cells passing through microporous membrane betweenδ-catenin+LY group and control group had no statistical significance(all P>0.05).Conclusionsδ-catenin may promote the enhancement of EMT and invasive ability of breast cancer cells by activating PI3K/AKT pathway.
作者 李占勇 刘志杰 李蕾 张俊毅 Li Zhanyong;Liu Zhijie;Li Lei;Zhang Junyi(Department of Pathology,Affiliated Hospital of Chifeng University,Chifeng 024000,China)
出处 《北京医学》 CAS 2022年第11期975-978,983,共5页 Beijing Medical Journal
基金 国家自然科学基金(81860507) 内蒙古自治区自然科学基金(2018MS08137) 内蒙古自治区高等学校青年科技英才支持计划(NJYT-20-A03)。
关键词 δ-catenin PI3K/AKT 上皮-间质转化 乳腺癌 δ-catenin PI3K/AKT epithelial-mesenchymal transition(EMT) breast cancer
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  • 1Pisick E, Jagadeesh S, Salgia R, et al. Receptor tyrosine kinases and inhibitors in lung cancer[J]. Sci World J, 2009, 6:589-604.
  • 2Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast and prostate cancer[J]. Science, 1997, 275:1943-1947.
  • 3Steelman LS, Bertrrand FE, McCubrey JA, et al. The complexity of PTEN: mutation, marker and potential target for therapeutic inter- vention[J]. Expert Opin Ther Targets, 2004, 8:537-550.
  • 4Sabatini DM. roTOR and cancer: insights into a complex relation- ship[J]. Nat Rev Can, 2006, 6:729-734.
  • 5Shaw R J, Cantley LC. Ras PI (3)K and roTOR signalling controls tumour cell growth[J]. Nature, 2006, 441:424-430.
  • 6Massion PP, Tafian PM, Shyr Y, et al. Early involvement of the phosphatidylinositol 3-kinase /Akt pathway in lung cancer pro- gression[J]. Am J Respir Crit Care Med, 2004, 170:1088-1094.
  • 7Conde E, Angulo B, Tang M, et al. Molecular context of the EGFR mutations: evidence for the activation of mTOR/S6K sig- naling[J]. Clin Cancer Res, 2006, 12:710-717.
  • 8Dudek H, Datta SR, Franke TF, et al. Regulation of neuronal sur- vival by the serine-threonine protein kinase Akt [J]. Science, 1997, 275:661-665.
  • 9Tamura M, Gu I, Takino T, et al. Tumor suppressor PTEN inhibi- tion of cell invision, migration, and growth: differential involve- ment of focal adhesion kinase and pl30cas [J]. Cancer Res, 2008, 59:442-449.
  • 10Lira WT, Zhang WH, Miller CR, et al. PTEN and phosphorylated AKT expression and prognosis in early-and late-stage non-small cell lung cancer[J]. Oncology Rep, 2007, 17:853-857.

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