膀胱癌组织中高表达的MTA2促进膀胱癌细胞T24的恶性生物学行为
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摘要
目的:分析肿瘤转移相关蛋白(MTA2)在人膀胱癌组织中的表达及其对膀胱癌细胞系T24恶性生物学行为的影响,探讨MTA2对膀胱癌进展中的作用。方法:收集河北省人民医院2012年12月至2014年12月收治的62例膀胱癌患者癌组织和28例正常膀胱组织(取自膀胱炎患者,病理学诊断为正常组织)标本,通过免疫组织化学染色检测膀胱癌和正常膀胱组织中MTA2的表达水平;分析MTA2表达水平与患者临床病理特征的相关性。构建稳定高表达MTA2的膀胱癌T24细胞系,通过MTS、克隆形成、划痕愈合和Transwell实验检测MTA2对膀胱癌T24细胞增殖、克隆形成、迁移和侵袭能力的影响。结果:与正常膀胱组织相比,膀胱癌组织中MTA2呈明显高表达(P<0.01);MTA2的高表达状态与膀胱癌患者的性别、年龄、肿瘤体积无关(P>0.05),而与患者更高的TNM分期、肿瘤的组织学分级、淋巴浸润和转移有关(均P<0.05)。在膀胱癌T24细胞系中过表达MTA2后,细胞的增殖活性明显升高(P<0.05),克隆形成、划痕愈合、迁移和侵袭能力均明显增强(均P<0.01)。结论:MTA2在人膀胱癌组织中表达上调,能够促进T24细胞增殖、克隆形成、迁移及侵袭等恶性生物学行为。
Objective: To investigate the expression of metastasis-associated protein 2(MTA2) in human bladder cancer tissues and its effect on the malignant biological behaviors of bladder cancer T24 cells, as well as to explore the effect of MTA2 on the progression of bladder cancer. Methods: Sixty-two cases of human bladder cancer tissues and 28 cases of normal bladder tissues(from patients with cystitis, and pathologically confirmed as normal tissue) were collected at People's Hospital of Hebei Province during December2012 and December 2014. The expression of MTA2 in bladder cancer tissues and normal bladder tissues was detected by immunohistochemical staining, and the correlation between MTA2 expression and clinicopathological characteristics of patients was also analyzed.The bladder cancer T24 cell line stably expressing MTA2 was constructed. The effects of MTA2 on the proliferation, colony formation,migration and invasion of bladder cancer T24 cells were detected by MTS, clone formation, scratch healing and Transwell assay, respectively. Results: Immunohistochemical staining showed that MTA2 expression was significantly up-regulated in bladder cancer tissues as compared with normal bladder tissues(P<0.01). The high expression of MTA2 in bladder cancer tissues was not related to gender,age and tumor volume(P>0.05), but was associated with higher TNM stage, histological grade, and lymphatic infiltration and metastasis(all P<0.05). After over-expression of MTA2 in bladder cancer T24 cell line, the proliferation activity of the cells was significantly increased(P<0.05), and the colony formation, scratch healing, migration and invasion ability were significantly increased(all P<0.01).Conclusions: MTA2 is up-regulated in human bladder cancer tissues and can promote the proliferation, tumor formation, migration and invasion of T24 cells.
Objective: To investigate the expression of metastasis-associated protein 2(MTA2) in human bladder cancer tissues and its effect on the malignant biological behaviors of bladder cancer T24 cells, as well as to explore the effect of MTA2 on the progression of bladder cancer. Methods: Sixty-two cases of human bladder cancer tissues and 28 cases of normal bladder tissues(from patients with cystitis, and pathologically confirmed as normal tissue) were collected at People's Hospital of Hebei Province during December2012 and December 2014. The expression of MTA2 in bladder cancer tissues and normal bladder tissues was detected by immunohistochemical staining, and the correlation between MTA2 expression and clinicopathological characteristics of patients was also analyzed.The bladder cancer T24 cell line stably expressing MTA2 was constructed. The effects of MTA2 on the proliferation, colony formation,migration and invasion of bladder cancer T24 cells were detected by MTS, clone formation, scratch healing and Transwell assay, respectively. Results: Immunohistochemical staining showed that MTA2 expression was significantly up-regulated in bladder cancer tissues as compared with normal bladder tissues(P<0.01). The high expression of MTA2 in bladder cancer tissues was not related to gender,age and tumor volume(P>0.05), but was associated with higher TNM stage, histological grade, and lymphatic infiltration and metastasis(all P<0.05). After over-expression of MTA2 in bladder cancer T24 cell line, the proliferation activity of the cells was significantly increased(P<0.05), and the colony formation, scratch healing, migration and invasion ability were significantly increased(all P<0.01).Conclusions: MTA2 is up-regulated in human bladder cancer tissues and can promote the proliferation, tumor formation, migration and invasion of T24 cells.
引文
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[16]ZHANG M,REN B,LI Z,et al.Expression of N-myc downstreamregulated gene 2 in bladder cancer and its potential utility as a urinary diagnostic biomarker[J/OL].Med Sci Monit,2017,23:4644-4649[2019-02-22].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627538/.
[17]WANG Y,KANG X L,ZENG F C,et al.Correlations of Foxo3 and Foxo4 expressions with clinicopathological features and prognosis of bladder cancer[J].Pathol Res Pract,2017,213(7):766-772.DOI:10.1016/j.prp.2017.04.004.
[18]SAIDI S,POPOV Z,JANEVSKA V,et al.Overexpression of UHRF1 gene correlates with the major clinicopathological parameters in urinary bladder cancer[J/OL].Int Braz J Urol,2017,43(2):224-229[2019-02-22].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433360/.DOI:10.1590/S1677-5538.IBJU.2016.0126.
[19]ZHU S,DENG S J,HE C,et al.Reciprocal loop of hypoxia-inducible factor-1α(HIF-1α)and metastasis-associated protein 2(MTA2)contributes to the progression of pancreatic carcinoma by suppressing E-cadherin transcription[J].J Pathol,2018,245(3):349-360.DOI:10.1002/path.5089.
[20]ZHANG B,TAO F,ZHANG H.Metastasis-associated protein 2 promotes the metastasis of non-small cell lung carcinoma by regulating the ERK/AKT and VEGF signaling pathways[J].Mol Med Report,2018,17(4):4899-4908.DOI:10.3892/mmr.2018.8535.
[2]陈晓芳,陈万青,周薇薇,等.2013年中国膀胱癌发病和死亡流行状况分析[J].中国肿瘤,2018,27(2):81-85.DOI:10.11735/j.issn.1004-0242.2018.02.A001.
[3]BOWEN N J,FUJITA N,KAJITA M,et al.Mi-2/NuRD:multiple complexes for many purposes[J].Biochim Biophys Acta,2004,1677(1/2/3):52-57.DOI:10.1016/j.bbaexp.2003.10.010.
[4]ZHOU C F,JI J,CAI Q,et al.MTA2 promotes gastric cancer cells invasion and is transcriptionally regulated by Sp1[J/OL].Mol Cancer,2013,12(1):102[2019-02-22].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851872/.DOI:10.1186/1476-4598-12-102.
[5]LIU Y P,SHAN B E,WANG X L,et al.Correlation between MTA2overexpression and tumour progression in esophageal squamous cell carcinoma[J/OL].Exp Ther Med,2012,3(4):745-749[2019-02-22].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438547/.DOI:10.3892/etm.2012.475.
[6]李秀娟,李明霞,赵轶峰,等.食管鳞癌组织MTA2表达与淋巴管生成关系探讨[J].中华肿瘤防治杂志,2014,21(9):674-677.DOI:10.3969/j.issn.1673-5269.2014.09.007.
[7]DING W J,HU W,YANG H H,et al.Prognostic correlation between MTA2 expression level and colorectal cancer[J/OL].Int J Clin Exp Pathol,2015,8(6):7173-7180[2019-02-22].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4525945/.
[8]侯蕊,申兴斌,张志勇.MTA2在结肠癌中的表达及意义的研究[J].临床和实验医学杂志,2015,14(8):620-622.DOI:10.3969/j.issn.1671-4695.2015.08.004.
[9]CHEN D W,FAN Y F,LI J,et al.MTA2 expression is a novel prognostic marker for pancreatic ductal adenocarcinoma[J].Tumour Biol,2013,34(3):1553-1557.DOI:10.1007/s13277-013-0685-3.
[10]王术华,齐艳丽,张俊毅,等.MTA2在非小细胞肺癌中的表达及意义[J].中国肺癌杂志,2010,13(8):777-780.DOI:10.3779/j.issn.1009-3419.2010.08.05.
[11]ZHANG B,ZHANG H,SHEN G.Metastasis-associated protein 2(MTA2)promotes the metastasis of non-small-cell lung cancer through the inhibition of the cell adhesion molecule Ep-CAM and E-cadherin[J/OL].Jpn J Clin Oncol,2016,46(4):393[2019-02-22].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886142/.DOI:10.1093/jjco/hyw010.
[12]霍海峰,范宗宪,牟嘉砾,等.MTA-2蛋白在喉鳞癌中的表达及其临床意义[J].现代肿瘤医学,2012,20(9):1809-1812.DOI:10.3969/j.issn.1672-4992.2012.09.15.
[13]JI Y X,ZHANG P,LU Y P,et al.Expression of MTA2 gene in ovarian epithelial cancer and its clinical implication[J].J Huazhong Univ Sci Technol Med Sci,2006,26(3):359-362.
[14]LU J,JIN M L.Short-hairpin RNA-mediated MTA2 silencing inhibits human breast cancer cell line MDA-MB231 proliferation and metastasis[J].Asian Pac J Cancer Prev,2014,15(14):5577-5582.
[15]陈磊,郑树艳,黄永望.MTA2对喉癌细胞系Hep-2的增殖、迁移和侵袭的影响[J].中国实验诊断学,2015,19(6):883-885.
[16]ZHANG M,REN B,LI Z,et al.Expression of N-myc downstreamregulated gene 2 in bladder cancer and its potential utility as a urinary diagnostic biomarker[J/OL].Med Sci Monit,2017,23:4644-4649[2019-02-22].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627538/.
[17]WANG Y,KANG X L,ZENG F C,et al.Correlations of Foxo3 and Foxo4 expressions with clinicopathological features and prognosis of bladder cancer[J].Pathol Res Pract,2017,213(7):766-772.DOI:10.1016/j.prp.2017.04.004.
[18]SAIDI S,POPOV Z,JANEVSKA V,et al.Overexpression of UHRF1 gene correlates with the major clinicopathological parameters in urinary bladder cancer[J/OL].Int Braz J Urol,2017,43(2):224-229[2019-02-22].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433360/.DOI:10.1590/S1677-5538.IBJU.2016.0126.
[19]ZHU S,DENG S J,HE C,et al.Reciprocal loop of hypoxia-inducible factor-1α(HIF-1α)and metastasis-associated protein 2(MTA2)contributes to the progression of pancreatic carcinoma by suppressing E-cadherin transcription[J].J Pathol,2018,245(3):349-360.DOI:10.1002/path.5089.
[20]ZHANG B,TAO F,ZHANG H.Metastasis-associated protein 2 promotes the metastasis of non-small cell lung carcinoma by regulating the ERK/AKT and VEGF signaling pathways[J].Mol Med Report,2018,17(4):4899-4908.DOI:10.3892/mmr.2018.8535.