The E-cadherin repressor slug and progression of human extrahepatic hilar cholangiocarcinoma

<p>Abstract</p> <p>Objectives</p> <p>This study explored the expression and function of Slug in human extrahepatic hilar cholangiocarcinoma (EHC) to identify its role in tumor progression.</p> <p>Methods</p> <p>The expression of Snail and Slug mR...

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Main Authors: Wang Xin-sheng, Li Chun-wei, Jiao Xue-long, Zhang Shao-yan, Wang Dong-sheng, Zhang Ke-jun, Yu Qin-chao, Cui Hai-ning
Format: Article
Language:English
Published: BMC 2010-07-01
Series:Journal of Experimental & Clinical Cancer Research
Online Access:http://www.jeccr.com/content/29/1/88
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author Wang Xin-sheng
Li Chun-wei
Jiao Xue-long
Zhang Shao-yan
Wang Dong-sheng
Zhang Ke-jun
Yu Qin-chao
Cui Hai-ning
author_facet Wang Xin-sheng
Li Chun-wei
Jiao Xue-long
Zhang Shao-yan
Wang Dong-sheng
Zhang Ke-jun
Yu Qin-chao
Cui Hai-ning
author_sort Wang Xin-sheng
collection DOAJ
description <p>Abstract</p> <p>Objectives</p> <p>This study explored the expression and function of Slug in human extrahepatic hilar cholangiocarcinoma (EHC) to identify its role in tumor progression.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>
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spelling doaj.art-0269f94814c8437585cb25fad0a0c18b2022-12-22T01:18:25ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662010-07-012918810.1186/1756-9966-29-88The E-cadherin repressor slug and progression of human extrahepatic hilar cholangiocarcinomaWang Xin-shengLi Chun-weiJiao Xue-longZhang Shao-yanWang Dong-shengZhang Ke-junYu Qin-chaoCui Hai-ning<p>Abstract</p> <p>Objectives</p> <p>This study explored the expression and function of Slug in human extrahepatic hilar cholangiocarcinoma (EHC) to identify its role in tumor progression.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>http://www.jeccr.com/content/29/1/88
spellingShingle Wang Xin-sheng
Li Chun-wei
Jiao Xue-long
Zhang Shao-yan
Wang Dong-sheng
Zhang Ke-jun
Yu Qin-chao
Cui Hai-ning
The E-cadherin repressor slug and progression of human extrahepatic hilar cholangiocarcinoma
Journal of Experimental & Clinical Cancer Research
title The E-cadherin repressor slug and progression of human extrahepatic hilar cholangiocarcinoma
title_full The E-cadherin repressor slug and progression of human extrahepatic hilar cholangiocarcinoma
title_fullStr The E-cadherin repressor slug and progression of human extrahepatic hilar cholangiocarcinoma
title_full_unstemmed The E-cadherin repressor slug and progression of human extrahepatic hilar cholangiocarcinoma
title_short The E-cadherin repressor slug and progression of human extrahepatic hilar cholangiocarcinoma
title_sort e cadherin repressor slug and progression of human extrahepatic hilar cholangiocarcinoma
url http://www.jeccr.com/content/29/1/88
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