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Estrogen Induces Selective Transcription of Caveolin1 Variants in Human Breast Cancer through Estrogen Responsive Element-Dependent Mechanisms

The estrogen receptor (ER) signaling regulates numerous physiological processes mainly through activation of gene transcription (genomic pathways). Caveolin1 (CAV1) is a membrane-resident protein that behaves as platform to enable different signaling molecules and receptors for membrane-initiated pa...

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Autores principales: Romano, Antonella, Feola, Antonia, Porcellini, Antonio, Gigantino, Vincenzo, Di Bonito, Maurizio, Di Mauro, Annabella, Caggiano, Rocco, Faraonio, Raffaella, Zuchegna, Candida
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503496/
https://www.ncbi.nlm.nih.gov/pubmed/32825330
http://dx.doi.org/10.3390/ijms21175989
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author Romano, Antonella
Feola, Antonia
Porcellini, Antonio
Gigantino, Vincenzo
Di Bonito, Maurizio
Di Mauro, Annabella
Caggiano, Rocco
Faraonio, Raffaella
Zuchegna, Candida
author_facet Romano, Antonella
Feola, Antonia
Porcellini, Antonio
Gigantino, Vincenzo
Di Bonito, Maurizio
Di Mauro, Annabella
Caggiano, Rocco
Faraonio, Raffaella
Zuchegna, Candida
author_sort Romano, Antonella
collection PubMed
description The estrogen receptor (ER) signaling regulates numerous physiological processes mainly through activation of gene transcription (genomic pathways). Caveolin1 (CAV1) is a membrane-resident protein that behaves as platform to enable different signaling molecules and receptors for membrane-initiated pathways. CAV1 directly interacts with ERs and allows their localization on membrane with consequent activation of ER-non-genomic pathways. Loss of CAV1 function is a common feature of different types of cancers, including breast cancer. Two protein isoforms, CAV1α and CAV1β, derived from two alternative translation initiation sites, are commonly described for this gene. However, the exact transcriptional regulation underlying CAV1 expression pattern is poorly elucidated. In this study, we dissect the molecular mechanism involved in selective expression of CAV1β isoform, induced by estrogens and downregulated in breast cancer. Luciferase assays and Chromatin immunoprecipitation demonstrate that transcriptional activation is triggered by estrogen-responsive elements embedded in CAV1 intragenic regions and DNA-binding of estrogen-ER complexes. This regulatory control is dynamically established by local chromatin changes, as proved by the occurrence of histone H3 methylation/demethylation events and association of modifier proteins as well as modification of H3 acetylation status. Thus, we demonstrate for the first time, an estrogen-ERs-dependent regulatory circuit sustaining selective CAV1β expression.
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spelling pubmed-75034962020-09-23 Estrogen Induces Selective Transcription of Caveolin1 Variants in Human Breast Cancer through Estrogen Responsive Element-Dependent Mechanisms Romano, Antonella Feola, Antonia Porcellini, Antonio Gigantino, Vincenzo Di Bonito, Maurizio Di Mauro, Annabella Caggiano, Rocco Faraonio, Raffaella Zuchegna, Candida Int J Mol Sci Article The estrogen receptor (ER) signaling regulates numerous physiological processes mainly through activation of gene transcription (genomic pathways). Caveolin1 (CAV1) is a membrane-resident protein that behaves as platform to enable different signaling molecules and receptors for membrane-initiated pathways. CAV1 directly interacts with ERs and allows their localization on membrane with consequent activation of ER-non-genomic pathways. Loss of CAV1 function is a common feature of different types of cancers, including breast cancer. Two protein isoforms, CAV1α and CAV1β, derived from two alternative translation initiation sites, are commonly described for this gene. However, the exact transcriptional regulation underlying CAV1 expression pattern is poorly elucidated. In this study, we dissect the molecular mechanism involved in selective expression of CAV1β isoform, induced by estrogens and downregulated in breast cancer. Luciferase assays and Chromatin immunoprecipitation demonstrate that transcriptional activation is triggered by estrogen-responsive elements embedded in CAV1 intragenic regions and DNA-binding of estrogen-ER complexes. This regulatory control is dynamically established by local chromatin changes, as proved by the occurrence of histone H3 methylation/demethylation events and association of modifier proteins as well as modification of H3 acetylation status. Thus, we demonstrate for the first time, an estrogen-ERs-dependent regulatory circuit sustaining selective CAV1β expression. MDPI 2020-08-20 /pmc/articles/PMC7503496/ /pubmed/32825330 http://dx.doi.org/10.3390/ijms21175989 Text en © 2020 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
Romano, Antonella
Feola, Antonia
Porcellini, Antonio
Gigantino, Vincenzo
Di Bonito, Maurizio
Di Mauro, Annabella
Caggiano, Rocco
Faraonio, Raffaella
Zuchegna, Candida
Estrogen Induces Selective Transcription of Caveolin1 Variants in Human Breast Cancer through Estrogen Responsive Element-Dependent Mechanisms
title Estrogen Induces Selective Transcription of Caveolin1 Variants in Human Breast Cancer through Estrogen Responsive Element-Dependent Mechanisms
title_full Estrogen Induces Selective Transcription of Caveolin1 Variants in Human Breast Cancer through Estrogen Responsive Element-Dependent Mechanisms
title_fullStr Estrogen Induces Selective Transcription of Caveolin1 Variants in Human Breast Cancer through Estrogen Responsive Element-Dependent Mechanisms
title_full_unstemmed Estrogen Induces Selective Transcription of Caveolin1 Variants in Human Breast Cancer through Estrogen Responsive Element-Dependent Mechanisms
title_short Estrogen Induces Selective Transcription of Caveolin1 Variants in Human Breast Cancer through Estrogen Responsive Element-Dependent Mechanisms
title_sort estrogen induces selective transcription of caveolin1 variants in human breast cancer through estrogen responsive element-dependent mechanisms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503496/
https://www.ncbi.nlm.nih.gov/pubmed/32825330
http://dx.doi.org/10.3390/ijms21175989
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