The in vitro influences of epidermal growth factor and heregulin-β1 on the efficacy of trastuzumab used in Her-2 positive breast adenocarcinoma

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dc.contributor.author Hurrell, Tracey
dc.contributor.author Outhoff, Kim
dc.date.accessioned 2014-02-17T10:00:23Z
dc.date.available 2014-02-17T10:00:23Z
dc.date.issued 2013-10-11
dc.description.abstract BACKGROUND: Human epidermal growth factor receptor-2 (Her-2) is over expressed in approximately 25-30% of all primary breast tumors resulting in a distinctive breast cancer subtype associated with a poor prognosis and a decrease in overall survival. Trastuzumab (Herceptin®), an anti-Her-2 monoclonal antibody, has dramatically altered the prognosis of Her-2 positive breast cancer. Trastuzumab is, however, associated with primary and acquired resistance. AIM AND METHODS: To investigate the in-vitro effects of trastuzumab on cell viability (tetrazolium conversion assay), cell cycling (propidium iodide staining), apoptosis (executioner caspases and annexin-V) and relative surface Her-2 receptor expression (anti-Her-2 affibody molecule) in Her-2-positive (SK-Br-3) and oestrogen receptor positive (MCF-7) breast adenocarcinoma cells and to determine potential augmentation of these effects by two endogenous ligands, epidermal growth factor (EGF) and heregulin-β1 (HRG- β1). RESULTS: Cell viability was decreased in SK-Br-3 cells by exposure to trastuzumab. This was associated with G1 accumulation and decreased relative surface Her-2 receptor density, supporting the cytostatic nature of trastuzumab in vitro. SK-Br-3 cells exposed to EGF and heregulin-β1 produced differential cell responses alone and in combination with trastuzumab, in some instances augmenting cell viability and cell cycling. Relative surface Her-2 receptor density was reduced substantially by trastuzumab, EGF and heregulin-β1. These reductions were amplified when ligands were used in combination with trastuzumab. CONCLUSION: Cell type specific interactions of endogenous ligands appear to be dependent on absolute Her-receptor expression and cross activation of signaling pathways. This supports the notion that receptor density of Her-family members and multiplicity of growth ligands are of mutual importance in breast cancer cell proliferation and therefore also in resistance associated with trastuzumab. en_US
dc.description.librarian am2014 en_US
dc.description.librarian ay2014
dc.description.sponsorship The authors would like to acknowledge Roche Pharmaceuticals for the donation of trastuzumab and the Cancer Association of South Africa (CANSA) and the Research and Development Programme (RDP), University of Pretoria, for providing funding. en_US
dc.description.uri http://www.cancerci.com/content/13/1/97 en_US
dc.identifier.citation Hurrell and Outhoff: The in vitro influences of epidermal growth factor and heregulin-β1 on the efficacy of trastuzumab used in Her-2 positive breast adenocarcinoma. Cancer Cell International 2013 13:97. en_US
dc.identifier.issn 1475-2867 (print)
dc.identifier.issn 1475-2867 (online)
dc.identifier.uri http://hdl.handle.net/2263/33485
dc.language.iso en en_US
dc.publisher BioMed Central en_US
dc.rights © 2013 Hurrell and Outhoff; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License en_US
dc.subject Trastuzumab en_US
dc.subject Heregulin-β1 en_US
dc.subject SK-Br-3 cells en_US
dc.subject Human epidermal growth factor receptor-2 (HER-2) en_US
dc.subject Epidermal growth factor (EGF) en_US
dc.subject.lcsh Breast -- Cancer -- Research en
dc.title The in vitro influences of epidermal growth factor and heregulin-β1 on the efficacy of trastuzumab used in Her-2 positive breast adenocarcinoma en_US
dc.type Article en_US


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