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dc.contributor.authorWang, Qi
dc.contributor.authorGün, Melisa
dc.contributor.authorHong, Xing-yu
dc.date.accessioned2019-12-23T14:08:45Z
dc.date.available2019-12-23T14:08:45Z
dc.date.issued2019en_US
dc.identifier.citationWang, Q., Gün, M. ve Hong, X. (2019). Induced tamoxifen resistance is mediated by increased methylation of e-cadherin in estrogen receptor-expressing breast cancer cells. Scientific Reports, 9. https://doi.org/10.1038/s41598-019-50749-1en_US
dc.identifier.issn2045-2322
dc.identifier.urihttps://doi.org/10.1038/s41598-019-50749-1
dc.identifier.urihttps://hdl.handle.net/20.500.12511/4623
dc.description.abstractEstrogen receptor-positive breast cancers are treated with tamoxifen, a drug that competitively inhibits the binding of estrogen to its receptor. Resistance to tamoxifen is a major hurdle in effective management of target breast cancer patient population. A number of dynamic changes within the tumor microenvironment, including the phenomenon of epithelial to mesenchymal transition (EMT), determine the response to endocrine therapy. EMT is marked by silencing or suppression of epithelial marker, E-Cadherin and we found significantly down-regulated E-Cadherin, among other epithelial markers, and a significantly up-regulated mesenchymal marker, Twist, among other mesenchymal markers, in a model system that comprised of tamoxifen sensitive MCF-7 cells and their tamoxifen-resistant counterparts, MCF-7-TAM, developed by chronic and escalating exposure of parental cells to tamoxifen. Further, E-cadherin, but not Twist, was differentially expressed in MCF-7-TAM cells because of differential methylation. Treatment with demethylating agent 5-azacytidine increased the expression of E-cadherin thus verifying a role of methylation in its silencing and, moreover, 5-azacytidine treatment also re-sensitized MCF-7-TAM cells to tamoxifen, as evaluated by assays for viability, apoptosis and migration potential. The 5-azacytidine effects were similar to effects of E-cadherin overexpression in MCF-7-TAM cells. This work describes novel mechanism of E-cadherin downregulation in tamoxifen resistant breast cancer cells. Further studies are needed to exploit this information for betterment of breast cancer therapy.en_US
dc.language.isoengen_US
dc.publisherNature Publishing Groupen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectEpithelial-Mesenchymal Transitionen_US
dc.subjectStem-Cellsen_US
dc.subjectMechanismsen_US
dc.subjectAgentsen_US
dc.titleInduced tamoxifen resistance is mediated by increased methylation of e-cadherin in estrogen receptor-expressing breast cancer cellsen_US
dc.typearticleen_US
dc.relation.journalScientific Reportsen_US
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesien_US
dc.identifier.volume9en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.doi10.1038/s41598-019-50749-1en_US


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