胃癌KRT17表达及其对上皮间质转化的影响

KRT17 expression in gastric cancer associated with epithelial-mesenchymal transition

目的:研究KRT17在胃癌组织、细胞的表达及其对上皮间质转化(epithelial mesenchymal transition,EMT)的作用。方法:利用RT-PCR法检测32对配对胃癌及癌旁组织KRT17的表达。用RT-PCR及Western印迹法检测胃癌细胞株与永生化胃黏膜上皮细胞KRT17的表达。免疫组织化学染色法评估227例胃癌组织芯片KRT17表达,结合临床病理资料进行初步分析。Transwell实验观察干扰KRT17的胃癌细胞与对照组细胞迁移、侵袭能力的差异。RT-PCR及Western印迹法检测EMT标志物E钙黏蛋白、波形蛋白的表达。结果 :KRT17在胃癌组织和细胞中表达显著增加,其表达高低与肿瘤组织分级(P=0.008),肿瘤浸润深度(T分期)(P=0.027),淋巴结转移(N分期)(P=0.03)密切相关。干扰KRT17后胃癌细胞迁移和侵袭能力明显下降,E钙黏蛋白的表达明显升高,波形蛋白的表达明显降低。结论:KRT17在胃癌组织中高表达,并与临床病理密切相关。KRT17下调后抑制细胞迁移与侵袭,通过抑制EMT的机制产生作用。

Objective To investigate the expression of KRT17 in gastric cancer tissues and cell lines, and the effect of KRT17 on epithelial mesenchymal transition（EMT） in gastric cancer. Methods The m RNA expression of KRT17 in gastric cancer was detected using 32 paired tissues of gastric cancer with adjacent gastric mucosa tissues by RT-PCR assay.KRT17 expression was analyzed in gastric cancer cell lines and immortalized gastric epithelial cell lines as control with RT-PCR and Western blot. Immunohistochemical staining was done to evaluate KRT 17 expression in 227 patients with gastric cancer on tissue microarray and analysis was performed with clinical and pathological data. Transwell assay was used to observe cell migration and invasion capacity in gastric cancer cells and in control cells. The expression of E-cadherin and vimentin（the markers of EMT） were detected with RT-PCR and Western blot after silencing of KRT17 in gastric cancer cell lines. Results Compared with adjacent gastric mucosa tissues, the expression of KRT17 in gastric cancer tissues up-regulated notably. KRT17 expression correlated with histological grade（P=0.008）, depth of invasion（P=0.027）,lymph node metastasis（P=0.03） remarkably. The migration and invasion decreased significantly in gastric cancer cells after silencing of KRT17 compared with control cells. E-cadherin expression increased and vimentin expression decreased significantly at both m RNA and protein level after silencing KRT17. Conclusions KRT17 was over-expressed in gastric cancer tissues and the expression of KRT17 had correlation with clinicopathological features. Down-regulation of KRT17 in gastric cancer may inhibit the migration and invasion of gastric cancer cells with EMT process.