锌指转录因子Snai1通过E-钙黏蛋白调控胃癌侵袭及淋巴结转移
Snai1, a zinc-finger transcriptional factor, induces gastric carcinoma invasion and metastasis via suppression of E-cadherin expression
摘要目的 探讨锌指转录因子Snai1在胃癌发生发展中的作用,以及胃癌组织中Snai1与E-钙黏蛋白(E-cadherin)表达的关系.方法 收集本院普外科2010年1月至2012年1月收治的65例胃癌患者手术切除的胃癌组织及邻近的正常胃黏膜组织,免疫组织化学检测Snai1和E-cadherin的表达.体外培养人胃腺癌细胞株SGC-7901,分为3组:空白对照组不进行转染,阴性对照组转染不含靶向作用于Snai1的siRNA的空质粒,转染组转染靶向作用于Snai1的siRNA.转染结束后实时定量PCR和免疫印迹法检测3组细胞Snai1和E-cadherin的表达.结果 胃癌组织中Snai1表达阳性率较正常胃黏膜组织明显增高(58.5%比0.0%,P<0.001),而E-cadherin表达阳性率明显降低(43.1%比100.0%,P<0.001).Snai1阳性和阴性的胃癌组织中E-cadherin表达的阳性率分别为28.9% (11/38)、63.0%(17/27).Snai1阳性的胃癌患者较Snai1阴性的胃癌患者淋巴结转移率明显升高(78.9%比40.7%,P<0.001).体外细胞实验显示,空白对照组与阴性对照组比较,Snai1和E-cadherin的表达差异无统计学意义(均P>0.05);与空白对照组比较,转染组Snai1 mRNA和蛋白表达下调,而E-cadherin mRNA和蛋白表达上调(均P<0.05).结论 Snai1可通过抑制E-cadherin表达,促进胃癌发生局部浸润及淋巴结转移.
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abstractsObjective To investigate the role of Snai1,the zinc finger transcriptional factor,in the pathogenesis of gastric carcinoma,and to examine the relationship between Snai 1 and E-cadherin expression.Methods The specimens of primary gastric carcinoma and adjacent normal gastric mucosa derived from 65 patients with gastric carcinoma who underwent gastrectomy between January 2010 and January 2012 in the department of gastroenterology of our hospital were subjected to immunohistochemistry assay for the measurement of Snai1 and E-cadherin expression.By using real-time polymerase chain reaction and Western blotting,the expression of Snai1 and E-cadherin in SGC-7901,a gastric cancer cell line,incubated in vitro,was quantified.This cell line was assigned to blank control group (untransfected with plasmids),negative control group (transfected with blank siRNA vector without Snai1 gene sequence) and SGC-7901-siRNA group (transfected with siRNA vector),respectively.Results Gastric carcinoma tissues yielded markedly higher Snai 1 expression (58.5% vs 0.0%,P<0.001) yet significantly lower E-cadherin expression (43.1% vs 100.0%,P<0.O01) than normal gastric mucosa.The positivity of E-cadherin was 28.9% (11/38) and 63.0% (12/27) in Snai1-positive and-negative specimens.The rate of lymph node metastasis was markedly higher in Snai1-positive than that in Snai1-negative cases (78.9% vs 40.7%,P<0.001).In vitro cell experiments suggested an unremarkable difference between Snai 1 and E-cadherin expression between blank control group and negative control group (P>0.05).Compared with blank control group,the SGC-7901-siRNA group was characterized by pronouncedly attenuated Snai1 mRNA and protein expression and considerably up-regulated E-cadherin mRNA and protein expression (all P<0.05).Conclusion Snai1 promotes focal infiltration and lymph node metastasis of gastric carcinoma via inhibition of E-cadherin expression .
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