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BMC Cancer

, 11:45

First Online: 31 January 2011Received: 05 January 2010Accepted: 31 January 2011DOI: 10.1186-1471-2407-11-45

Cite this article as: Gostner, J.M., Fong, D., Wrulich, O.A. et al. BMC Cancer 2011 11: 45. doi:10.1186-1471-2407-11-45

Abstract

BackgroundRecently, 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.

MethodsIn 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.

ResultsFor the first time we could show that expression profiling data of EpCAM transfected cell lines Hs578T and MDA-MB-231 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-231 but not Hs578T cells. In Hs578T cells, an increase of proliferation and chemosensitivity to Docetaxel was associated with EpCAM overexpression.

ConclusionsThese 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.

List of abbreviationsbHLHbasic-helix-loop-helix

CAMcellular adhesion molecule

c-mycv-myc myelocytomatosis viral oncogene homolog

E-FABPepidermal fatty acid binding protein

EpCAMepithelial cell adhesion molecule

EpICDEpCAM intracellular domain

FHL2four and a half LIM-only protein 2

SFRPsecreted frizzeled related protein

GAPDHglyceraldehyde-3-phosphate dehydrogenase

IRESinternal ribosome entry site

LEFlymphoid enhancer binding factor

SDS-PAGEsodium dodecylsulfate polyacrylamide gel electrophoresis; Wnt pathway wingless-type MMTV integration site family signaling pathway

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-11-45 contains supplementary material, which is available to authorized users.

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Autor: Johanna M Gostner - Dominic Fong - Oliver A Wrulich - Florian Lehne - Marion Zitt - Martin Hermann - Sylvia Krobitsch - A

Fuente: https://link.springer.com/







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