Cargando…
Effects of EpCAM overexpression on human breast cancer cell lines
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...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042418/ https://www.ncbi.nlm.nih.gov/pubmed/21281469 http://dx.doi.org/10.1186/1471-2407-11-45 |
_version_ | 1782198545481203712 |
---|---|
author | Gostner, Johanna M Fong, Dominic Wrulich, Oliver A Lehne, Florian Zitt, Marion Hermann, Martin Krobitsch, Sylvia Martowicz, Agnieszka Gastl, Guenther Spizzo, Gilbert |
author_facet | Gostner, Johanna M Fong, Dominic Wrulich, Oliver A Lehne, Florian Zitt, Marion Hermann, Martin Krobitsch, Sylvia Martowicz, Agnieszka Gastl, Guenther Spizzo, Gilbert |
author_sort | Gostner, Johanna M |
collection | PubMed |
description | 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 Hs578T(EpCAM )and MDA-MB-231(EpCAM )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. |
format | Text |
id | pubmed-3042418 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-30424182011-02-22 Effects of EpCAM overexpression on human breast cancer cell lines Gostner, Johanna M Fong, Dominic Wrulich, Oliver A Lehne, Florian Zitt, Marion Hermann, Martin Krobitsch, Sylvia Martowicz, Agnieszka Gastl, Guenther Spizzo, Gilbert BMC Cancer Research Article 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 Hs578T(EpCAM )and MDA-MB-231(EpCAM )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. BioMed Central 2011-01-31 /pmc/articles/PMC3042418/ /pubmed/21281469 http://dx.doi.org/10.1186/1471-2407-11-45 Text en Copyright ©2011 Gostner et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Gostner, Johanna M Fong, Dominic Wrulich, Oliver A Lehne, Florian Zitt, Marion Hermann, Martin Krobitsch, Sylvia Martowicz, Agnieszka Gastl, Guenther Spizzo, Gilbert Effects of EpCAM overexpression on human breast cancer cell lines |
title | Effects of EpCAM overexpression on human breast cancer cell lines |
title_full | Effects of EpCAM overexpression on human breast cancer cell lines |
title_fullStr | Effects of EpCAM overexpression on human breast cancer cell lines |
title_full_unstemmed | Effects of EpCAM overexpression on human breast cancer cell lines |
title_short | Effects of EpCAM overexpression on human breast cancer cell lines |
title_sort | effects of epcam overexpression on human breast cancer cell lines |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042418/ https://www.ncbi.nlm.nih.gov/pubmed/21281469 http://dx.doi.org/10.1186/1471-2407-11-45 |
work_keys_str_mv | AT gostnerjohannam effectsofepcamoverexpressiononhumanbreastcancercelllines AT fongdominic effectsofepcamoverexpressiononhumanbreastcancercelllines AT wrulicholivera effectsofepcamoverexpressiononhumanbreastcancercelllines AT lehneflorian effectsofepcamoverexpressiononhumanbreastcancercelllines AT zittmarion effectsofepcamoverexpressiononhumanbreastcancercelllines AT hermannmartin effectsofepcamoverexpressiononhumanbreastcancercelllines AT krobitschsylvia effectsofepcamoverexpressiononhumanbreastcancercelllines AT martowiczagnieszka effectsofepcamoverexpressiononhumanbreastcancercelllines AT gastlguenther effectsofepcamoverexpressiononhumanbreastcancercelllines AT spizzogilbert effectsofepcamoverexpressiononhumanbreastcancercelllines |