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Interaction of ERα and NRF2 Impacts Survival in Ovarian Cancer Patients
Nuclear factor erythroid 2-related factor 2 (NRF2) regulates cytoprotective antioxidant processes. In this study, the prognostic potential of NRF2 and its interactions with the estrogen receptor α (ERα) in ovarian cancer cells was investigated. NRF2 and ERα protein expression in ovarian cancer tissu...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337731/ https://www.ncbi.nlm.nih.gov/pubmed/30597961 http://dx.doi.org/10.3390/ijms20010112 |
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author | Czogalla, Bastian Kahaly, Maja Mayr, Doris Schmoeckel, Elisa Niesler, Beate Kolben, Thomas Burges, Alexander Mahner, Sven Jeschke, Udo Trillsch, Fabian |
author_facet | Czogalla, Bastian Kahaly, Maja Mayr, Doris Schmoeckel, Elisa Niesler, Beate Kolben, Thomas Burges, Alexander Mahner, Sven Jeschke, Udo Trillsch, Fabian |
author_sort | Czogalla, Bastian |
collection | PubMed |
description | Nuclear factor erythroid 2-related factor 2 (NRF2) regulates cytoprotective antioxidant processes. In this study, the prognostic potential of NRF2 and its interactions with the estrogen receptor α (ERα) in ovarian cancer cells was investigated. NRF2 and ERα protein expression in ovarian cancer tissue was analyzed as well as mRNA expression of NRF2 (NFE2L2) and ERα (ESR1) in four ovarian cancer and one benign cell line. NFE2L2 silencing was carried out to evaluate a potential interplay between NRF2 and ERα. Cytoplasmic NRF2 expression as inactive form had significantly higher expression in patients with low-grade histology (p = 0.03). In the serous cancer subtype, high cytoplasmic NRF2 expression (overall survival (OS), median 50.6 vs. 29.3 months; p = 0.04) and high ERα expression (OS, median 74.5 vs. 27.1 months; p = 0.002) was associated with longer overall survival as well as combined expression of both inactive cytoplasmic NRF2 and ERα in the whole cohort (median 74.5 vs. 37.7 months; p = 0.04). Cytoplasmic NRF2 expression showed a positive correlation with ERα expression (p = 0.004). NFE2L2 was found to be highly expressed in the ovarian cancer cell lines OVCAR3, UWB1.289, and TOV112D. Compared with the benign cell line HOSEpiC, ESR1 expression was reduced in all ovary cancer cell lines (all p < 0.001). Silencing of NFE2L2 induced a higher mRNA expression of ESR1 in the NFE2L2 downregulated cancer cell lines OVCAR3 (p = 0.003) and ES2 (p < 0.001), confirming genetic interactions of NRF2 and ERα. In this study, both inactive cytoplasmic NRF2 and high ERα expression were demonstrated to be associated with improved survival in ovarian cancer patients. Further understanding of interactions within the estradiol–ERα–NRF2 pathway could better predict the impact of endocrine therapy in ovarian cancer. |
format | Online Article Text |
id | pubmed-6337731 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63377312019-01-22 Interaction of ERα and NRF2 Impacts Survival in Ovarian Cancer Patients Czogalla, Bastian Kahaly, Maja Mayr, Doris Schmoeckel, Elisa Niesler, Beate Kolben, Thomas Burges, Alexander Mahner, Sven Jeschke, Udo Trillsch, Fabian Int J Mol Sci Article Nuclear factor erythroid 2-related factor 2 (NRF2) regulates cytoprotective antioxidant processes. In this study, the prognostic potential of NRF2 and its interactions with the estrogen receptor α (ERα) in ovarian cancer cells was investigated. NRF2 and ERα protein expression in ovarian cancer tissue was analyzed as well as mRNA expression of NRF2 (NFE2L2) and ERα (ESR1) in four ovarian cancer and one benign cell line. NFE2L2 silencing was carried out to evaluate a potential interplay between NRF2 and ERα. Cytoplasmic NRF2 expression as inactive form had significantly higher expression in patients with low-grade histology (p = 0.03). In the serous cancer subtype, high cytoplasmic NRF2 expression (overall survival (OS), median 50.6 vs. 29.3 months; p = 0.04) and high ERα expression (OS, median 74.5 vs. 27.1 months; p = 0.002) was associated with longer overall survival as well as combined expression of both inactive cytoplasmic NRF2 and ERα in the whole cohort (median 74.5 vs. 37.7 months; p = 0.04). Cytoplasmic NRF2 expression showed a positive correlation with ERα expression (p = 0.004). NFE2L2 was found to be highly expressed in the ovarian cancer cell lines OVCAR3, UWB1.289, and TOV112D. Compared with the benign cell line HOSEpiC, ESR1 expression was reduced in all ovary cancer cell lines (all p < 0.001). Silencing of NFE2L2 induced a higher mRNA expression of ESR1 in the NFE2L2 downregulated cancer cell lines OVCAR3 (p = 0.003) and ES2 (p < 0.001), confirming genetic interactions of NRF2 and ERα. In this study, both inactive cytoplasmic NRF2 and high ERα expression were demonstrated to be associated with improved survival in ovarian cancer patients. Further understanding of interactions within the estradiol–ERα–NRF2 pathway could better predict the impact of endocrine therapy in ovarian cancer. MDPI 2018-12-29 /pmc/articles/PMC6337731/ /pubmed/30597961 http://dx.doi.org/10.3390/ijms20010112 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Czogalla, Bastian Kahaly, Maja Mayr, Doris Schmoeckel, Elisa Niesler, Beate Kolben, Thomas Burges, Alexander Mahner, Sven Jeschke, Udo Trillsch, Fabian Interaction of ERα and NRF2 Impacts Survival in Ovarian Cancer Patients |
title | Interaction of ERα and NRF2 Impacts Survival in Ovarian Cancer Patients |
title_full | Interaction of ERα and NRF2 Impacts Survival in Ovarian Cancer Patients |
title_fullStr | Interaction of ERα and NRF2 Impacts Survival in Ovarian Cancer Patients |
title_full_unstemmed | Interaction of ERα and NRF2 Impacts Survival in Ovarian Cancer Patients |
title_short | Interaction of ERα and NRF2 Impacts Survival in Ovarian Cancer Patients |
title_sort | interaction of erα and nrf2 impacts survival in ovarian cancer patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337731/ https://www.ncbi.nlm.nih.gov/pubmed/30597961 http://dx.doi.org/10.3390/ijms20010112 |
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