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dc.contributor.author Luzhna, Lidiya
dc.contributor.author Lykkesfeldt, Anne E.
dc.contributor.author Kovalchuk, Olga
dc.date.accessioned 2019-01-23T22:05:28Z
dc.date.available 2019-01-23T22:05:28Z
dc.date.issued 2015
dc.identifier.citation Luzhna, L., Lykkesfeldt, A. E., & Kovalchuk, O. (2015). Altered radiation responses of breast cancer cells resistant to hormonal therapy. Oncotarget, 6(3), 1678-1694. https://doi.org/10.18632/oncotarget.3188 en_US
dc.identifier.uri https://hdl.handle.net/10133/5274
dc.description Sherpa Romeo blue journal. Open access article. Creative Commons Attribution 3.0 License (CC BY 3.0) applies. en_US
dc.description.abstract Endocrine therapy agents (the selective estrogen receptor (ER) modulators such as tamoxifen or the selective ER down-regulators such as ICI 182,780) are key treatment regimens for hormone receptor-positive breast cancers. While these drugs are very effective in controlling ER-positive breast cancer, many tumors that initially respond well to treatment often acquire drug resistance, which is a major clinical problem. In clinical practice, hormonal therapy agents are commonly used in combination or sequence with radiation therapy. Tamoxifen treatment and radiotherapy improve both local tumor control and patient survival. However, tamoxifen treatment may render cancer cells less responsive to radiation therapy. Only a handful of data exist on the effects of radiation on cells resistant to hormonal therapy agents. These scarce data show that cells that were resistant to tamoxifen were also resistant to radiation. Yet, the existence and mechanisms of cross-resistance to endocrine therapy and radiation therapy need to be established. Here, we for the first time examined and compared radiation responses of MCF-7 breast adenocarcinoma cells (MCF-7/S0.5) and two antiestrogen resistant cell lines derived from MCF-7/S0.5: the tamoxifen resistant MCF-7/TAMR-1 and ICI 182,780 resistant MCF-7/182R-6 cell lines. Specifically, we analyzed the radiation-induced changes in the expression of genes involved in DNA damage, apoptosis, and cell cycle regulation. We found that the tamoxifen-resistant cell line in contrast to the parental and ICI 182,780-resistant cell lines displayed a significantly less radiationinduced decrease in the expression of genes involved in DNA repair. Furthermore, we show that MCF-7/TAMR-1 and MCF-7/182R-6 cells were less susceptible to radiation-induced apoptosis as compared to the parental line. These data indicate that tamoxifen-resistant breast cancer cells have a reduced sensitivity to radiation treatment. The current study may therefore serve as a roadmap to the future analysis of the mechanisms of cross-resistance between hormonal therapy and radiation. en_US
dc.language.iso en_US en_US
dc.publisher Impact Journals en_US
dc.subject Breast cancer en_US
dc.subject Endocrine therapy en_US
dc.subject Radiation en_US
dc.subject Transcriptomics en_US
dc.subject Apoptosis en_US
dc.subject Treatment resistance en_US
dc.subject Drug resistance en_US
dc.subject.lcsh Radiotherapy
dc.subject.lcsh Tamoxifen
dc.subject.lcsh Breast--Cancer
dc.subject.lcsh Breast--Cancer--Research
dc.title Altered radiation responses of breast cancer cells resistant to hormonal therapy en_US
dc.type Article en_US
dc.publisher.faculty Arts and Science en_US
dc.publisher.department Department of Biological Sciences en_US
dc.description.peer-review Yes en_US
dc.publisher.institution University of Lethbridge en_US
dc.publisher.institution Danish Cancer Society Research Center en_US


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