Snail调控乳腺癌细胞中MTDH表达机制的研究

doi:10.3969/j.issn.1000-8535.2015.06.001

摘要/Abstract

摘要： 目的分析乳腺癌细胞中Snail与MTDH基因的作用,明确Snail是否通过结合于MTDH的启动子区域促进乳腺癌转移。方法克隆、转染Snail基因至乳腺癌细胞,观察过表达Snail的乳腺癌细胞中MTDHmRNA及蛋白表达的变化;再使用免疫共沉淀法检测Snail与MTDH基因的共作用。结果转染Snail基因进入乳腺癌MDA-MB-435细胞后,转染组、空白组和对照组中MTDHmRNA的表达水平分别为1.61±0.22、1.02±0.18、0.99±0.20,转染组高于空白组和对照组,差异有统计学意义(P<0.05),而后两组表达无差异(P>0.05);Westren blot检测结果显示,Snail可促进MTDH蛋白的表达;免疫共沉淀显示,Snail与MTDH在细胞内存在相互结合作用。结论 Snail在乳腺癌细胞中可通过结合于MTDH基因的启动子区域,促进MTDHmRNA转录及相关蛋白的表达,从而导致乳腺癌转移。

关键词: Snail, 乳腺癌, MTDH

Abstract: Objective To investigate the function of Snail to MTDH gene in breast cancer cells. Methods We observed the changement of MTDHmRNA and protein expression in breast cancer cell line MDA-MB-435 after transfected with Snail gene. Then, we used co-immunoprecipitation to determine the domain of Snail and MTDH binding in vitro. Results After transfected with Snail gene into MDA-MB-435 cell, the expression levels of MTDHmRNA in transfection group, blank group and control group were 1.61±0.22,1.02±0.18,0.99±0.20. The level of transfection group was significantly higher than the other groups(P< 0.05). Western blot showed that the expression of MTDH protein can be promoted by Snail. Co-immunoprecipitation showed that Snail and MTDH are binding interactions in breast cancer cell line MDA-MB-43. Conclusion Snail can promote transcription and expression of MTDH in breast cancer cells by binding to the promoter region of the MTDH gene resulting in metastasis of breast cancer.

Key words: Snail, Breast cancer, MTDH

方喜生, 刘国龙, 李宝秀, 曹小飞, 关明媚, 刘霞. Snail调控乳腺癌细胞中MTDH表达机制的研究[J]. 广州医药, 2015, 46(6): 1-3.

Fang Xisheng, Liu Guolong, Li Baoxiu, et al. Study on the regulate mechanism of Snail to the expression of MTDH in breast cancer cells[J]. Guangzhou Medical Journal, 2015, 46(6): 1-3.

参考文献

[1] Jemal A, Bray F, Center MM, et al. Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2): 69-90.
[2] Fritzenwanker JH, Saina M, Technau U. Analysis of forkhead and snail expression reveals epithelial-mesenchymal transition during embryonic and larval development of Nematostella vectensis[J]. Dev Biol, 2004,275(2):389-402.
[3] Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells[J]. Cell, 2008, 133(4): 704-715.
[4] Mallini P, Lennard T, Kirby J, et al. Epithelial-to-mesenchymal transition: what is the impact on breast cancer stem cells and drug resistance. Cancer Treat Rev, 2014, 40(3): 341-348.
[5] Anwar TE, Kleer CG. Tissue-based identification of stem cells and epithelial-to-mesenchymal transition in breast cancer[J]. Hum Pathol, 2013, 44(8): 1457-1464.
[6] Cho HJ, Park SM, Kim IK, et al. RhoGDI2 promotes epithelial-mesenchymal transition via induction of Snail in gastric cancer cells[J]. Oncotarget, 2014,5(6):1554-1564.
[7] Zhu M, Yin F, Fan X, et al. Decreased TIP30 promotes Snail-mediated epithelial-mesenchymal transition and tumor-initiating properties in hepatocellular carcinoma[J]. Oncogene,2015,34(11):1420-1431.
[8] Burton LJ, Barnett P, Smith B, et al. Muscadine grape skin extract reverts snail-mediated epithelial mesenchymal transition via superoxide species in human prostate cancer cells[J]. BMC Complement Altern Med, 2014(14): 97.
[9] Zhou W, Lv R, Qi W, et al. Snail contributes to the maintenance of stem cell-like phenotype cells in human pancreatic cancer[J]. PLoS One, 2014, 9(1): e87409.
[10] Muenst S, Daster S, Obermann EC, et al. Nuclear expression of snail is an independent negative prognostic factor in human breast cancer[J]. Dis Markers, 2013, 35(5): 337-344.
[11] Zhuo W, Wang Y, Zhuo X, et al. Knockdown of Snail, a novel zinc finger transcription factor, via RNA interference increases A549 cell sensitivity to cisplatin via JNK/mitochondrial pathway[J]. Lung Cancer, 2008,62(1):8-14.
[12] Hu G, Chong RA, Yang Q, et al. MTDH activation by 8q22 genomic gain promotes chemoresistance and metastasis of poor-prognosis breast cancer[J]. Cancer Cell, 2009,15(1):9-20.
[13] Qian BJ, Yan F, Li N, et al. MTDH/AEG-1-based DNA vaccine suppresses lung metastasis and enhances chemosensitivity to doxorubicin in breast cancer[J]. Cancer Immunol Immunother, 2011, 60(6): 883-893.
[14] Hu G, Chong RA, Yang Q, et al. MTDH activation by 8q22 genomic gain promotes chemoresistance and metastasis of poor-prognosis breast cancer[J]. Cancer Cell, 2009,15(1):9-20.

[1]	翁沛华. 超声-微泡介导miR-128通过调节PTEN抑制乳腺癌细胞阿霉素耐药[J]. 广州医药, 2021, 52(6): 35-38.
[2]	黎颂铭, 郝俊文, 洪云, 李良. 槐耳颗粒用于乳腺癌术后辅助化疗期对内分泌激素及生存期的影响[J]. 广州医药, 2021, 52(5): 109-112.
[3]	叶晔, 费伟强, 冯冠. SEER数据库中晚期三阴性乳腺癌的危险因素及预后分析[J]. 广州医药, 2021, 52(1): 26-34.
[4]	李淑怡, 黄玉珍, 蓝秀万. 乳腺癌关键基因的生物信息学分析[J]. 广州医药, 2021, 52(1): 65-71.
[5]	黄毅敏, 向炳辉, 王小锋, 岑川, 邓永康. 乳腺癌根治术中保留乳头乳晕对术后疗效、上肢功能及外观满意度的影响[J]. 广州医药, 2020, 51(1): 121-124.
[6]	许素真. 阿那曲唑和他莫昔芬治疗激素受体阳性绝经后转移性乳腺癌的疗效和安全性对比[J]. 广州医药, 2018, 49(6): 118-120.
[7]	魏宜霖, 柳建华, 杨毓雯. 乳腺癌超声多参数及临床病理学特点与腋窝淋巴结转移的关系[J]. 广州医药, 2018, 49(5): 89-93.
[8]	曾志坚, 陈玉兰, 邝碧茹, 练英妮, 李曙平. 6野切线射野方式用于左侧乳腺癌根治术后放疗的临床研究[J]. 广州医药, 2018, 49(4): 91-93.
[9]	王雷, 高琳璐. 乳腺癌组织中SIRT1的表达观察[J]. 广州医药, 2017, 48(4): 17-19.
[10]	雷叶青, 李海涛, 曹健, 何仕青, 王海裕, 黎春华, 许金凤. 卡培他滨单药维持治疗在晚期乳腺癌的疗效观察[J]. 广州医药, 2017, 48(3): 102-105.
[11]	金科, 朱剑梅, 邱发麒. BAG-1基因与乳腺癌TAM治疗敏感性的相关性研究[J]. 广州医药, 2017, 48(1): 5-8.
[12]	位红芹, 余美玲, 韦英丽, 肖妮娜, 柳建华. 微泡增强的超声空化对荷瘤兔乳腺癌作用效果的研究[J]. 广州医药, 2016, 47(2): 32-34.
[13]	叶志东, 黄迪, 黄宇, 张强, 麦振豪, 赵俐, 古维立. B超弹性成像监测下应用吉西他滨耐药乳腺癌细胞4T1构建裸鼠乳腺癌肝转移模型[J]. 广州医药, 2016, 47(1): 49-52.
[14]	张娇, 李燕英. 连续护理在提高乳腺癌保乳患者生存质量中的应用效果分析[J]. 广州医药, 2015, 46(6): 56-58.
[15]	黄迪, 叶志东, 黄宇, 张强, 龚振豪, 赵俐, 肖洪波, 古维立. 辅助内分泌治疗对乳腺癌患者血脂及肝功能水平的影响[J]. 广州医药, 2015, 46(6): 59-61.