Effects of EpCAM overexpression on human breast cancer cell lines

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• 作者：Johanna M Gostner (1)
  Dominic Fong (1) (2)
  Oliver A Wrulich (3)
  Florian Lehne (1)
  Marion Zitt (1)
  Martin Hermann (4)
  Sylvia Krobitsch (5)
  Agnieszka Martowicz (1)
  Guenther Gastl (1) (2)
  Gilbert Spizzo (1) (2) (6)
  
• 刊名：BMC Cancer
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：11
• 期：1
• 全文大小：2235KB
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  47. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/11/45/prepub
  
• 作者单位：Johanna M Gostner (1)
  Dominic Fong (1) (2)
  Oliver A Wrulich (3)
  Florian Lehne (1)
  Marion Zitt (1)
  Martin Hermann (4)
  Sylvia Krobitsch (5)
  Agnieszka Martowicz (1)
  Guenther Gastl (1) (2)
  Gilbert Spizzo (1) (2) (6)
  
  1. Laboratory for Experimental Oncology, Tyrolean Cancer Research Institute, Innrain 66, 6020, Innsbruck, Austria
  2. Department of Haematology and Oncology, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria
  3. Division of Medical Biochemistry, Biocenter Innsbruck Fritz, Pregl Strasse 3, 6020, Innsbruck, Austria
  4. KMT-Laboratory, Innrain 66, 6020, Innsbruck, Austria
  5. Max Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195, Berlin, Germany
  6. Department of Haematology and Oncology, Franz Tappeiner Hospital, Via Rossini 5, 39012, Merano, Italy
  
• ISSN：1471-2407

文摘

Background 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. Methods 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. Results 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 ?-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. Conclusions 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.