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The Peculiar Estrogenicity of Diethyl Phthalate: Modulation of Estrogen Receptor α Activities in the Proliferation of Breast Cancer Cells

Phthalates comprise a group of synthetic chemicals present in the environment because of their wide use as plasticizers and as additives in products for personal care. Among others, diethyl phthalate (DEP) is largely used in products for infants, children, and adults, in which its exposure has been...

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Autores principales: Fiocchetti, Marco, Bastari, Giovanna, Cipolletti, Manuela, Leone, Stefano, Acconcia, Filippo, Marino, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538674/
https://www.ncbi.nlm.nih.gov/pubmed/34678933
http://dx.doi.org/10.3390/toxics9100237
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author Fiocchetti, Marco
Bastari, Giovanna
Cipolletti, Manuela
Leone, Stefano
Acconcia, Filippo
Marino, Maria
author_facet Fiocchetti, Marco
Bastari, Giovanna
Cipolletti, Manuela
Leone, Stefano
Acconcia, Filippo
Marino, Maria
author_sort Fiocchetti, Marco
collection PubMed
description Phthalates comprise a group of synthetic chemicals present in the environment because of their wide use as plasticizers and as additives in products for personal care. Among others, diethyl phthalate (DEP) is largely used in products for infants, children, and adults, in which its exposure has been correlated with an increased risk of breast cancer. The adverse health outcomes deriving from phthalate exposure have been associated with their activity as endocrine disruptors (EDCs) of the steroid and thyroid hormone signaling by affecting developmental and reproductive health, and even carcinogenicity. However, the estrogen disruptor activities of DEP are still controversial, and the mechanism at the root of the estrogenic-disrupting action of DEP remains to be clarified. Here, we evaluated the DEP mechanism of action on the activation status of estrogen receptor α (ERα) by analyzing the receptor’s phosphorylation as well as both nuclear and extra-nuclear pathways triggered by the receptor to modulate the proliferation of breast cancer cells. Although DEP does not bind to ERα, our results suggest that this phthalate ester exerts multiple parallel interactions with ERα signaling and emphasize the importance to determine an appropriate battery of in vitro methods that will include specific molecular mechanisms involved in the endocrine disruption.
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spelling pubmed-85386742021-10-24 The Peculiar Estrogenicity of Diethyl Phthalate: Modulation of Estrogen Receptor α Activities in the Proliferation of Breast Cancer Cells Fiocchetti, Marco Bastari, Giovanna Cipolletti, Manuela Leone, Stefano Acconcia, Filippo Marino, Maria Toxics Article Phthalates comprise a group of synthetic chemicals present in the environment because of their wide use as plasticizers and as additives in products for personal care. Among others, diethyl phthalate (DEP) is largely used in products for infants, children, and adults, in which its exposure has been correlated with an increased risk of breast cancer. The adverse health outcomes deriving from phthalate exposure have been associated with their activity as endocrine disruptors (EDCs) of the steroid and thyroid hormone signaling by affecting developmental and reproductive health, and even carcinogenicity. However, the estrogen disruptor activities of DEP are still controversial, and the mechanism at the root of the estrogenic-disrupting action of DEP remains to be clarified. Here, we evaluated the DEP mechanism of action on the activation status of estrogen receptor α (ERα) by analyzing the receptor’s phosphorylation as well as both nuclear and extra-nuclear pathways triggered by the receptor to modulate the proliferation of breast cancer cells. Although DEP does not bind to ERα, our results suggest that this phthalate ester exerts multiple parallel interactions with ERα signaling and emphasize the importance to determine an appropriate battery of in vitro methods that will include specific molecular mechanisms involved in the endocrine disruption. MDPI 2021-09-25 /pmc/articles/PMC8538674/ /pubmed/34678933 http://dx.doi.org/10.3390/toxics9100237 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fiocchetti, Marco
Bastari, Giovanna
Cipolletti, Manuela
Leone, Stefano
Acconcia, Filippo
Marino, Maria
The Peculiar Estrogenicity of Diethyl Phthalate: Modulation of Estrogen Receptor α Activities in the Proliferation of Breast Cancer Cells
title The Peculiar Estrogenicity of Diethyl Phthalate: Modulation of Estrogen Receptor α Activities in the Proliferation of Breast Cancer Cells
title_full The Peculiar Estrogenicity of Diethyl Phthalate: Modulation of Estrogen Receptor α Activities in the Proliferation of Breast Cancer Cells
title_fullStr The Peculiar Estrogenicity of Diethyl Phthalate: Modulation of Estrogen Receptor α Activities in the Proliferation of Breast Cancer Cells
title_full_unstemmed The Peculiar Estrogenicity of Diethyl Phthalate: Modulation of Estrogen Receptor α Activities in the Proliferation of Breast Cancer Cells
title_short The Peculiar Estrogenicity of Diethyl Phthalate: Modulation of Estrogen Receptor α Activities in the Proliferation of Breast Cancer Cells
title_sort peculiar estrogenicity of diethyl phthalate: modulation of estrogen receptor α activities in the proliferation of breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538674/
https://www.ncbi.nlm.nih.gov/pubmed/34678933
http://dx.doi.org/10.3390/toxics9100237
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