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Targeting estrogen receptor beta (ERβ) for treatment of ovarian cancer: importance of KDM6B and SIRT1 for ERβ expression and functionality
Estrogen receptor (ER) β has growth inhibitory and chemo drug potentiating effect on ovarian cancer cells. We studied the dependence of ERβ function on the presence of KDM6B and SIRT1 in human ovarian cancer cells in vitro. Activation of ERβ with the subtype-selective agonist KB9520 resulted in sign...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833712/ https://www.ncbi.nlm.nih.gov/pubmed/29422491 http://dx.doi.org/10.1038/s41389-018-0027-9 |
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author | Pinton, Giulia Nilsson, Stefan Moro, Laura |
author_facet | Pinton, Giulia Nilsson, Stefan Moro, Laura |
author_sort | Pinton, Giulia |
collection | PubMed |
description | Estrogen receptor (ER) β has growth inhibitory and chemo drug potentiating effect on ovarian cancer cells. We studied the dependence of ERβ function on the presence of KDM6B and SIRT1 in human ovarian cancer cells in vitro. Activation of ERβ with the subtype-selective agonist KB9520 resulted in significant inhibition of human ovarian cancer cell growth. KB9520-activated ERβ had an additive effect on growth inhibition in combination with cisplatin and paclitaxel, respectively. Loss of KDM6B expression had a negative effect on ERβ function as a ligand-dependent inhibitor of ovarian cancer cell growth. In contrast, loss or inhibition of SIRT1 deacetylase activity restored ligand-activated ERβ functionality. Presented data suggest that selective targeting of ERβ with an agonist potentiate chemotherapy efficacy for the treatment of ovarian cancer and that downregulation or inhibition of SIRT1 may further enhance its therapeutic effect. |
format | Online Article Text |
id | pubmed-5833712 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58337122018-03-06 Targeting estrogen receptor beta (ERβ) for treatment of ovarian cancer: importance of KDM6B and SIRT1 for ERβ expression and functionality Pinton, Giulia Nilsson, Stefan Moro, Laura Oncogenesis Article Estrogen receptor (ER) β has growth inhibitory and chemo drug potentiating effect on ovarian cancer cells. We studied the dependence of ERβ function on the presence of KDM6B and SIRT1 in human ovarian cancer cells in vitro. Activation of ERβ with the subtype-selective agonist KB9520 resulted in significant inhibition of human ovarian cancer cell growth. KB9520-activated ERβ had an additive effect on growth inhibition in combination with cisplatin and paclitaxel, respectively. Loss of KDM6B expression had a negative effect on ERβ function as a ligand-dependent inhibitor of ovarian cancer cell growth. In contrast, loss or inhibition of SIRT1 deacetylase activity restored ligand-activated ERβ functionality. Presented data suggest that selective targeting of ERβ with an agonist potentiate chemotherapy efficacy for the treatment of ovarian cancer and that downregulation or inhibition of SIRT1 may further enhance its therapeutic effect. Nature Publishing Group UK 2018-02-09 /pmc/articles/PMC5833712/ /pubmed/29422491 http://dx.doi.org/10.1038/s41389-018-0027-9 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Pinton, Giulia Nilsson, Stefan Moro, Laura Targeting estrogen receptor beta (ERβ) for treatment of ovarian cancer: importance of KDM6B and SIRT1 for ERβ expression and functionality |
title | Targeting estrogen receptor beta (ERβ) for treatment of ovarian cancer: importance of KDM6B and SIRT1 for ERβ expression and functionality |
title_full | Targeting estrogen receptor beta (ERβ) for treatment of ovarian cancer: importance of KDM6B and SIRT1 for ERβ expression and functionality |
title_fullStr | Targeting estrogen receptor beta (ERβ) for treatment of ovarian cancer: importance of KDM6B and SIRT1 for ERβ expression and functionality |
title_full_unstemmed | Targeting estrogen receptor beta (ERβ) for treatment of ovarian cancer: importance of KDM6B and SIRT1 for ERβ expression and functionality |
title_short | Targeting estrogen receptor beta (ERβ) for treatment of ovarian cancer: importance of KDM6B and SIRT1 for ERβ expression and functionality |
title_sort | targeting estrogen receptor beta (erβ) for treatment of ovarian cancer: importance of kdm6b and sirt1 for erβ expression and functionality |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833712/ https://www.ncbi.nlm.nih.gov/pubmed/29422491 http://dx.doi.org/10.1038/s41389-018-0027-9 |
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