Cytoplasmic ERα and NFκB Promote Cell Survival in Mouse Mammary Cancer Cell Lines
Autor: | Jonna Frasor, Emily Smart, Luis H Alejo |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Selective Estrogen Receptor Modulators Cancer Research Programmed cell death Cytoplasm Antineoplastic Agents Hormonal Cell Survival Endocrinology Diabetes and Metabolism Dimethyl Fumarate Estrogen receptor Breast Neoplasms Biology Article 03 medical and health sciences Mice 0302 clinical medicine Endocrinology Cell Line Tumor medicine Animals Humans Cell Proliferation Endocrine and Autonomic Systems Cell growth Estrogen Receptor alpha NF-kappa B Mammary Neoplasms Experimental Disease Models Animal Oxidative Stress Tamoxifen 030104 developmental biology Oncology Cell culture Apoptosis 030220 oncology & carcinogenesis Cancer cell Cancer research MCF-7 Cells Female Signal transduction medicine.drug |
Zdroj: | Horm Cancer |
Popis: | 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. |
Databáze: | OpenAIRE |
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