摘要
目的:探究TWIST介导的上皮间质化(EMT)在宫颈癌发生发展中的作用。方法:选取正常宫颈上皮、宫颈上皮内瘤变以及宫颈鳞状细胞癌患者标本共128例,石蜡包埋连续切片并运用免疫组织化学的方法检测TWIST和E-cadherin在各组织中表达情况;构建TWIST真核表达载体pcD-NA3.1(+)/TWIST并建立高表达TWIST的宫颈癌细胞系pcDNA3.1(+)/TWIST/SiHa,观察稳转前后细胞形态学改变并运用蛋白质印迹法检测EMT相关标志蛋白变化。结果:TWIST在正常宫颈上皮、CINⅠ～Ⅱ、CINⅢ到早期宫颈鳞癌(ⅠA～ⅡA期)及晚期宫颈癌(ⅡB～ⅢB期)中胞质阳性表达率分别为14.2%、63.4%、64.3%、100.0%和100.0%;胞核阳性表达率分别为21.4%、56.6%、57.1%、88.0%和100.0%。与此同时,E-cadherin在各期组织中胞膜表达阳性率分别为71.4%、36.7%、35.7%、12.0%和11.1%,而胞质表达阳性率分别为18.6%、63.3%、64.3%、88.0%和88.9%。同时,TWIST在各期组织胞质、胞核表达强度改变与E-cadherin在胞膜、胞质表达分布及强度改变相反。在伴有淋巴结转移的宫颈癌病例中,TWIST在胞质胞核中的强阳性率高于不伴淋巴结转移病例(P=0.012,P=0.033),高表达TWIST的SiHa细胞系细胞形态及EMT相关标志蛋白E-cadherin和Vimentin均发生明显改变,差异有统计学意义,P<0.05。结论:TWIST在宫颈癌变发生发展的过程中表达逐渐升高,其介导的上皮间质转化贯穿宫颈癌发生发展的整个过程。
OBJECTIVE：To investigate the relationship of TWIST induced epithelial-mesenchymal transitions and cervical cancer progression.METHODS：Immunohistochemistry was used to examine the distribution and expression of TWIST and E-cadherin in 128specimens inclnding normal cervial tissue,cervical intraepithelial neoplasia（CIN） and squamous cell carcinoma of cervix（SCC）.To construct eukaryotic expression vector of human TWIST pcDNA3.1（＋）/ TWIST and establish its stable transfected SiHa cell line.The morphology of the cell line was observed and alteration of the EMT markers was tested by western blot.RESULTS：In specimens of normal cervial tissues,CINⅠ-Ⅱ,CINⅢ,SCC（ⅠA-ⅡA）,and SCC（ⅡB-ⅢB）,the positive expression of TWIST in cytoplasm were 14.2%,63.4%,64.3%,100.0%,100.0%,and in cell nucleus were 21.4%,56.6%,57.1%,88.0%,100.0%.In the same specimens,the positive expression of E-cadherin in cellular membrane were 71.4%,36.7%,35.7%,12.0%,11.1%,and in cytoplasm were 18.6%,63.3%,64.3%,88.0%,88.9%.The inverse correlation was obtained between the expression of TWIST and E-cadherin.The expression of TWIST in the SCC groups with lymph node metastasis were higher than that in the groups without lymph node metastasis（P=0.012,P=0.033）.The morphology of pcDNA3.1（＋）/ TWIST / SiHa cell line obviously transformed and expression of EMT markers had also changed（P0.05）.CONCLUSIONS：The expression of TWIST escalats during the tumorigenesis and progression of cervical cancer.Additionally,EMT induced by TWIST plays an important role in this process.
出处
《中华肿瘤防治杂志》
CAS
2011年第22期1741-1745,1801,共5页
Chinese Journal of Cancer Prevention and Treatment
基金
国家自然科学基金(81071663
072132)
