Altered radiation responses of breast cancer cells resistant to hormonal therapy

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dc.contributor.authorLuzhna, Lidiya
dc.contributor.authorLykkesfeldt, Anne E.
dc.contributor.authorKovalchuk, Olga
dc.date.accessioned2019-01-23T22:05:28Z
dc.date.available2019-01-23T22:05:28Z
dc.date.issued2015
dc.descriptionSherpa Romeo blue journal. Open access article. Creative Commons Attribution 3.0 License (CC BY 3.0) applies.en_US
dc.description.abstractEndocrine 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.description.peer-reviewYesen_US
dc.identifier.citationLuzhna, 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.3188en_US
dc.identifier.urihttps://hdl.handle.net/10133/5274
dc.language.isoen_USen_US
dc.publisherImpact Journalsen_US
dc.publisher.departmentDepartment of Biological Sciencesen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionUniversity of Lethbridgeen_US
dc.publisher.institutionDanish Cancer Society Research Centeren_US
dc.publisher.urlhttps://doi.org/10.18632/oncotarget.3188
dc.subjectBreast canceren_US
dc.subjectEndocrine therapyen_US
dc.subjectRadiationen_US
dc.subjectTranscriptomicsen_US
dc.subjectApoptosisen_US
dc.subjectTreatment resistanceen_US
dc.subjectDrug resistanceen_US
dc.subject.lcshRadiotherapy
dc.subject.lcshTamoxifen
dc.subject.lcshBreast--Cancer
dc.subject.lcshBreast--Cancer--Research
dc.titleAltered radiation responses of breast cancer cells resistant to hormonal therapyen_US
dc.typeArticleen_US
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