Transcriptional repressor snail and progression of human hepatocellular carcinoma.
Transcriptional repressor snail and progression of human hepatocellular carcinoma.
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发表时间：
2003-07
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通讯作者：
K. Sugimachi;Shinji Tanaka;T. Kameyama;K. Taguchi;S. Aishima;M. Shimada;K. Sugimachi;M. Tsuneyoshi
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作者：
K. Sugimachi;Shinji Tanaka;T. Kameyama;K. Taguchi;S. Aishima;M. Shimada;K. Sugimachi;M. Tsuneyoshi
Snail蛋白是一种抑制性E-钙粘蛋白转录因子，介导细胞间粘附、肿瘤进展和转移。我们探讨了Snail及其家族成员Slug在人肝细胞癌（HCC）中的表达和功能，以确定其在肿瘤进展中的作用。实验设计和结果在Li-7（内源性E-钙粘蛋白阳性的人HCC细胞）中转染Snail cDNA，选择性地诱导E-钙粘蛋白蛋白表达的丧失。然后，我们研究了Snail和Slug mRNA在43例人HCC组织样本中的表达。利用原位杂交，Snail mRNA被确定为主要表达在HCC细胞中，而不是在胆管细胞、血管或浸润的白细胞中。采用实时逆转录酶-PCR定量Snail和Slug的mRNA，并研究其与E-钙粘蛋白表达和临床病理因素的相关性。7例（16%）肝癌组织中Snail mRNA表达高于癌旁肝组织。免疫组化结果显示，Snail mRNA过表达组E-Cadherin蛋白表达明显下调（P = 0.04）。Snail mRNA阳性率与肿瘤浸润性独立相关（P = 0.04）。然而，Slug mRNA与E-钙粘蛋白表达和肿瘤侵袭性均不相关。结论Snail基因下调E-cadherin的表达，促进HCC的侵袭。
PURPOSE Snail protein is a suppressive transcriptional factor of E-cadherin that mediates cell-to-cell adhesion, tumor progression, and metastases. We explored the expression and function of Snail and its family member Slug in human hepatocellular carcinoma (HCC) to identify its role in tumor progression. EXPERIMENTAL DESIGN AND RESULTS Transfection of Snail cDNA in Li-7, endogenous E-cadherin-positive human HCC cells, selectively induced the loss of E-cadherin protein expression. We then investigated the expression of Snail and Slug mRNA in 43 human tissue samples of HCC. Using in situ hybridization, Snail mRNA was determined to dominantly express in HCC cells, but not in bile duct cells, blood vessels or infiltrating leukocytes. The mRNA of Snail and Slug were quantified using real-time reverse transcriptase-PCR, and correlations with E-cadherin expression and clinicopathological factors were investigated. Snail mRNA was overexpressed in 7 cases (16%) of HCC compared with adjacent noncancerous liver tissue. E-Cadherin protein expression determined in the same 43 cases by immunohistochemistry was significantly down-regulated in those cases with Snail mRNA overexpression (P = 0.04). The tumor and nontumor ratio of Snail mRNA independently correlated with tumor invasiveness (P = 0.04). However, Slug mRNA correlated with neither E-cadherin expression nor tumor invasiveness. CONCLUSIONS The data indicate that Snail both down-regulates E-cadherin expression and promotes the invasion in human HCC.