Effects of EpCAM overexpression on human breast cancer cell lines.
Effects of EpCAM overexpression on human breast cancer cell lines.
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DOI：
10.1186/1471-2407-11-45
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发表时间：
2011-01-31
期刊：
影响因子：
3.8
通讯作者：
Spizzo G
中科院分区：
文献类型：
--
作者：
Gostner JM;Fong D;Wrulich OA;Lehne F;Zitt M;Hermann M;Krobitsch S;Martowicz A;Gastl G;Spizzo G
最近，EpCAM作为基于抗体和疫苗的癌症免疫疗法的靶点引起了人们的极大兴趣。在乳腺癌中，EpCAM抗原在所有病例的30-40%中过表达，并且这种表达增加与不良预后相关。EpCAM特异性单克隆抗体的使用是这些患者中有希望的治疗方法。为了探索EpCAM过表达后的分子变化，我们研究了市售的人乳腺癌细胞系Hs 578 T和MDA-MB-231中EpCAM基因表达后转录组的变化。为了评估细胞增殖，进行基于四唑盐的测定。TCF/LEF报告试剂盒用于测量Wnt/β-连环蛋白途径的转录活性。为了评估β-连环蛋白在细胞核中的积累，进行了亚细胞分级分离测定。这是我们第一次发现EpCAM转染的细胞系Hs 578 TEpCAM和MDA-MB-231 EpCAM的表达谱数据表明EpCAM过表达与Wnt信号传导抑制剂SFRP 1和TCF 7 L2的下调有关。通过TCF/LEF报告试剂盒和通过发现MDA-MB-231 EpCAM而不是Hs 578 TEpCAM细胞的β-连环蛋白的核积累来证实增加的Wnt信号传导。在Hs 578 T细胞中，增殖和对多西紫杉醇的化疗敏感性的增加与EpCAM过表达相关。这些数据显示乳腺癌细胞系中EpCAM过表达后Wnt信号传导组分的细胞类型依赖性修饰，这导致边缘功能变化。进一步研究EpCAM与SFRP 1和TCF 7 L2的相互作用以及可能导致EpCAM过表达变化的其他因素，将有助于表征EpCAM阳性乳腺癌细胞的独特分子特性。
Recently, EpCAM has attracted major interest as a target for antibody- and vaccine-based cancer immunotherapies. In breast cancer, the EpCAM antigen is overexpressed in 30-40% of all cases and this increased expression correlates with poor prognosis. The use of EpCAM-specific monoclonal antibodies is a promising treatment approach in these patients. In order to explore molecular changes following EpCAM overexpression, we investigated changes of the transcriptome upon EpCAM gene expression in commercially available human breast cancer cells lines Hs578T and MDA-MB-231. To assess cell proliferation, a tetrazolium salt based assay was performed. A TCF/LEF Reporter Kit was used to measure the transcriptional activity of the Wnt/β-catenin pathway. To evaluate the accumulation of β-catenin in the nucleus, a subcellular fractionation assay was performed. For the first time we could show that expression profiling data of EpCAM transfected cell lines Hs578TEpCAM and MDA-MB-231EpCAM indicate an association of EpCAM overexpression with the downregulation of the Wnt signaling inhibitors SFRP1 and TCF7L2. Confirmation of increased Wnt signaling was provided by a TCF/LEF reporter kit and by the finding of the nuclear accumulation of ß-catenin for MDA-MB-231EpCAM but not Hs578TEpCAM cells. In Hs578T cells, an increase of proliferation and chemosensitivity to Docetaxel was associated with EpCAM overexpression. These data show a cell type dependent modification of Wnt signaling components after EpCAM overexpression in breast cancer cell lines, which results in marginal functional changes. Further investigations on the interaction of EpCAM with SFRP1 and TCF7L2 and on additional factors, which may be causal for changes upon EpCAM overexpression, will help to characterize unique molecular properties of EpCAM-positive breast cancer cells.
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影响因子：
168.9
作者：
Gastl, G;Spizzo, G;Mikuz, G
通讯作者：
Mikuz, G
DOI：
10.1083/jcb.139.5.1337
发表时间：
1997-12-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Litvinov SV;Balzar M;Winter MJ;Bakker HA;Briaire-de Bruijn IH;Prins F;Fleuren GJ;Warnaar SO
通讯作者：
Warnaar SO
影响因子：
11.2
作者：
Sankpal NV;Willman MW;Fleming TP;Mayfield JD;Gillanders WE
通讯作者：
Gillanders WE
影响因子：
3.7
作者：
Balzar, M;Prins, FA;Litvinov, SV
通讯作者：
Litvinov, SV
影响因子：
2.5
作者：
Hatsell, S;Rowlands, T;Cowin, P
通讯作者：
Cowin, P