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Discover Oncology
Published in: Discover Oncology 2/2020

01-04-2020 | Tamoxifen | Original Paper

Cytoplasmic ERα and NFκB Promote Cell Survival in Mouse Mammary Cancer Cell Lines

Authors: Emily Smart, Luis H. Alejo, Jonna Frasor

Published in: Discover Oncology | Issue 2/2020

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Abstract

There is a desperate need in the field for mouse mammary tumors and cell lines that faithfully mimic estrogen receptor (ER) expression and activity found in human breast cancers. We found that several mouse mammary cancer cell lines express ER but fail to demonstrate classical estrogen-driven proliferation or transcriptional activity. We investigated whether these cell lines may be used to model tamoxifen resistance by using small molecule inhibitors to signaling pathways known to contribute to resistance. We found that the combination of NFκB inhibition and ER antagonists significantly reduced cell proliferation in vitro, as well as growth of syngeneic tumors. Surprisingly, we found that ER was localized to the cytoplasm, regardless of any type of treatment. Based on this, we probed extra-nuclear functions of ER and found that co-inhibition of ER and NFκB led to an increase in oxidative stress and apoptosis. Together, these findings suggest that cytoplasmic ER and NFκB may play redundant roles in protecting mammary cancer cells from oxidative stress and cell death. Although this study has not identified a mouse model with classical ER activity, cytoplasmic ER has been described in a small subset of human breast tumors, suggesting that these findings may be relevant for some breast cancer patients.
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Metadata
Title
Cytoplasmic ERα and NFκB Promote Cell Survival in Mouse Mammary Cancer Cell Lines
Authors
Emily Smart
Luis H. Alejo
Jonna Frasor
Publication date
01-04-2020
Publisher
Springer US
Published in
Discover Oncology / Issue 2/2020
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-020-00378-2

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