General Surgery, the Affiliated Hospital of medical College, Qingdao University, Qing dao, Shandong Province, 266003, China.
J Exp Clin Cancer Res. 2010 Jul 1;29(1):88. doi: 10.1186/1756-9966-29-88.
This study explored the expression and function of Slug in human extrahepatic hilar cholangiocarcinoma (EHC) to identify its role in tumor progression.
The expression of Snail and Slug mRNA in 52 human tissue samples of EHC was investigated. The mRNA of Snail and Slug were quantified using reverse transcriptase-PCR, and correlations with E-cadherin expression and clinicopathological factors were investigated. We then investigated transfection of Slug cDNA in endogenous E-cadherin-positive human EHC FRH0201 cells, selectively induced the loss of E-cadherin protein expression, and then small interfering RNA (siRNA) for inhibition of Slug expression in endogenous Slug-positive human EHC QBC939 cells, selectively induced the loss of Slug protein expression. A Boyden chamber transwell assay was used for invasion.
Slug mRNA was overexpressed in 18 cases (34.6%) of EHC compared with adjacent noncancerous tissue. E-Cadherin protein expression determined in the same 52 cases by immunohistochemistry was significantly down-regulated in those cases with Slug mRNA overexpression (P = 0.0001). The tumor and nontumor ratio of Slug mRNA was correlated with nodal metastasis(p = 0.0102), distant metastasis (p = 0.0001)and Survival time(p = 0.0443). However, Snail mRNA correlated with neither E-cadherin expression nor tumor invasiveness. By inhibiting Slug expression by RNA interference, we found that reduced Slug levels upregulated E-cadherin and decreased invasion in QBC939 cell. When the QBC939 cells was infected with Slug cDNA,, significant E-cadherin was downregulated and increased invasion in QBC939 cell.
The results suggested that Slug expression plays an important role in both the regulation of E-cadherin expression and in the acquisition of invasive potential in human EHC. Slug is possibly a potential target for an antitumor therapy blocking the functions of invasion and metastasis in human EHCs.
本研究旨在探讨 Slug 在人肝外胆管癌（EHC）中的表达和功能，以明确其在肿瘤进展中的作用。
检测 52 例 EHC 组织标本中 Slug 和 SnailmRNA 的表达。采用逆转录-PCR 定量检测 Slug 和 SnailmRNA，分析其与 E-钙黏蛋白表达及临床病理因素的相关性。然后，在 E-钙黏蛋白阳性的人 EHC FRH0201 细胞中转染 Slug cDNA，选择性诱导 E-钙黏蛋白蛋白表达缺失，同时在 Slug 阳性的人 EHC QBC939 细胞中用小干扰 RNA（siRNA）抑制 Slug 表达，选择性诱导 Slug 蛋白表达缺失。采用 Boyden 室小室侵袭实验检测侵袭能力。
与相邻非癌组织相比，18 例（34.6%）EHC 中 SlugmRNA 表达上调。对 52 例标本进行免疫组化检测，结果显示 SlugmRNA 表达上调与 E-钙黏蛋白蛋白表达缺失显著相关（P=0.0001）。SlugmRNA 肿瘤/非肿瘤比值与淋巴结转移（p=0.0102）、远处转移（p=0.0001）和生存时间（p=0.0443）显著相关。然而，SnailmRNA 与 E-钙黏蛋白表达和肿瘤侵袭性均无相关性。通过 RNA 干扰抑制 Slug 表达，我们发现 QBC939 细胞中 Slug 水平降低可上调 E-钙黏蛋白表达并降低侵袭性。而当 QBC939 细胞感染 Slug cDNA 时，E-钙黏蛋白表达显著下调，侵袭性增强。
这些结果表明 Slug 表达在调节 E-钙黏蛋白表达和获得人 EHC 侵袭潜能方面发挥重要作用。Slug 可能是阻断人 EHC 侵袭转移功能的抗肿瘤治疗的潜在靶点。
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