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

dc.contributor.authorHurrell, Tracey
dc.contributor.authorOuthoff, Kim
dc.contributor.emailtracey.hurrell@up.ac.zaen_US
dc.date.accessioned2014-02-17T10:00:23Z
dc.date.available2014-02-17T10:00:23Z
dc.date.issued2013-10-11
dc.description.abstractBACKGROUND: 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.librarianam2014en_US
dc.description.librarianay2014
dc.description.sponsorshipThe 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.urihttp://www.cancerci.com/content/13/1/97en_US
dc.identifier.citationHurrell 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.issn1475-2867 (print)
dc.identifier.issn1475-2867 (online)
dc.identifier.urihttp://hdl.handle.net/2263/33485
dc.language.isoenen_US
dc.publisherBioMed Centralen_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 Licenseen_US
dc.subjectTrastuzumaben_US
dc.subjectHeregulin-β1en_US
dc.subjectSK-Br-3 cellsen_US
dc.subjectHuman epidermal growth factor receptor-2 (HER-2)en_US
dc.subjectEpidermal growth factor (EGF)en_US
dc.subject.lcshBreast -- Cancer -- Researchen
dc.titleThe in vitro influences of epidermal growth factor and heregulin-β1 on the efficacy of trastuzumab used in Her-2 positive breast adenocarcinomaen_US
dc.typeArticleen_US

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