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Published on: February 8, 2013
Effects of EpCAM overexpression on human breast cancer cell lines
Johanna M Gostner1, Dominic Fong, Oliver A Wrulich
1Laboratory for Experimental Oncology, Tyrolean Cancer Research Institute, Innrain 66, 6020 Innsbruck, Austria.
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 ß-catenin for MDA-MB-231 EpCAM but not Hs578T EpCAM 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.
Insights
EpCAM overexpression in breast cancer cells alters Wnt signaling and can increase proliferation and chemosensitivity. These findings offer insights into EpCAM-positive breast cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Immunotherapy
Background:
- Epithelial cell adhesion molecule (EpCAM) is a target for cancer immunotherapies.
- EpCAM is overexpressed in 30-40% of breast cancers, correlating with poor prognosis.
- EpCAM-specific monoclonal antibodies represent a promising therapeutic strategy.
Purpose of the Study:
- To investigate molecular changes associated with EpCAM overexpression in breast cancer.
- To explore the impact of EpCAM on Wnt/β-catenin signaling.
- To assess functional consequences such as proliferation and chemosensitivity.
Main Methods:
- Gene expression analysis in EpCAM-transfected breast cancer cell lines (Hs578T, MDA-MB-231).
- Tetrazolium salt assay for cell proliferation assessment.
- TCF/LEF Reporter Kit and subcellular fractionation to evaluate Wnt/β-catenin pathway activity and nuclear β-catenin accumulation.
Main Results:
- EpCAM overexpression correlated with downregulation of Wnt signaling inhibitors SFRP1 and TCF7L2.
- Increased Wnt signaling was confirmed by reporter assays and nuclear β-catenin accumulation in MDA-MB-231 EpCAM cells.
- Hs578T EpCAM cells showed increased proliferation and chemosensitivity to Docetaxel.
Conclusions:
- EpCAM overexpression induces cell type-dependent modifications in Wnt signaling components.
- Functional changes observed were marginal, suggesting complex regulatory mechanisms.
- Further research is needed to elucidate EpCAM interactions and identify factors driving EpCAM-positive breast cancer cell properties.
