Effects of EpCAM overexpression on human breast cancer cell lines

  • Gostner J
  • Fong D
  • Wrulich O
 et al. 
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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/�-catenin pathway. To evaluate the accumulation of �-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.

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  • Johanna Gostner

  • Dominic Fong

  • Oliver Wrulich

  • Florian Lehne

  • Marion Zitt

  • Martin Hermann

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