CCAAT/enhancer binding protein β (C/EBPβ) isoforms as transcriptional regulators of the pro-invasive CDH3/P-cadherin gene in human breast cancer cells.

P-cadherin is a cell-cell adhesion molecule codified by the CDH3 gene, which expression is highly associated with undifferentiated cells in normal adult epithelial tissues, as well as with poorly differentiated carcinomas. In breast cancer, P-cadherin is frequently overexpressed in high-grade tumour...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: André Albergaria, Carlos Resende, Ana Rita Nobre, Ana Sofia Ribeiro, Bárbara Sousa, José Carlos Machado, Raquel Seruca, Joana Paredes, Fernando Schmitt
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2013
Materias:
R
Q
Acceso en línea:https://doaj.org/article/11611a12228544b6af36f2dd13996a77
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:11611a12228544b6af36f2dd13996a77
record_format dspace
spelling oai:doaj.org-article:11611a12228544b6af36f2dd13996a772021-11-18T07:58:31ZCCAAT/enhancer binding protein β (C/EBPβ) isoforms as transcriptional regulators of the pro-invasive CDH3/P-cadherin gene in human breast cancer cells.1932-620310.1371/journal.pone.0055749https://doaj.org/article/11611a12228544b6af36f2dd13996a772013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23405208/?tool=EBIhttps://doaj.org/toc/1932-6203P-cadherin is a cell-cell adhesion molecule codified by the CDH3 gene, which expression is highly associated with undifferentiated cells in normal adult epithelial tissues, as well as with poorly differentiated carcinomas. In breast cancer, P-cadherin is frequently overexpressed in high-grade tumours and is a well-established indicator of aggressive tumour behaviour and poor patient prognosis. However, till now, the mechanisms controlling CDH3 gene activation have been poorly explored. Since we recently described the existence of several CCAAT/Enhancer Binding Protein β (C/EBPβ) transcription factor binding sites at the CDH3 promoter, the aim of this study was to assess if the distinct C/EBPβ isoforms were directly involved in the transcriptional activation of the CDH3 gene in breast cancer cells. DNA-protein interactions, mutation analysis and luciferase reporter assay studies have been performed. We demonstrated that C/EBPβ is co-expressed with P-cadherin in breast cancer cells and all the three isoforms function as transcriptional regulators of the CDH3 gene, directly interacting with specific regions of its promoter. Interestingly, this transcriptional activation was only reflected at the P-cadherin protein level concerning the LIP isoform. Taken together, our data show that CDH3 is a newly defined transcriptional target gene of C/EBPβ isoforms in breast cancer, and we also identified the binding sites that are relevant for this activation.André AlbergariaCarlos ResendeAna Rita NobreAna Sofia RibeiroBárbara SousaJosé Carlos MachadoRaquel SerucaJoana ParedesFernando SchmittFernando SchmittPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e55749 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
André Albergaria
Carlos Resende
Ana Rita Nobre
Ana Sofia Ribeiro
Bárbara Sousa
José Carlos Machado
Raquel Seruca
Joana Paredes
Fernando Schmitt
Fernando Schmitt
CCAAT/enhancer binding protein β (C/EBPβ) isoforms as transcriptional regulators of the pro-invasive CDH3/P-cadherin gene in human breast cancer cells.
description P-cadherin is a cell-cell adhesion molecule codified by the CDH3 gene, which expression is highly associated with undifferentiated cells in normal adult epithelial tissues, as well as with poorly differentiated carcinomas. In breast cancer, P-cadherin is frequently overexpressed in high-grade tumours and is a well-established indicator of aggressive tumour behaviour and poor patient prognosis. However, till now, the mechanisms controlling CDH3 gene activation have been poorly explored. Since we recently described the existence of several CCAAT/Enhancer Binding Protein β (C/EBPβ) transcription factor binding sites at the CDH3 promoter, the aim of this study was to assess if the distinct C/EBPβ isoforms were directly involved in the transcriptional activation of the CDH3 gene in breast cancer cells. DNA-protein interactions, mutation analysis and luciferase reporter assay studies have been performed. We demonstrated that C/EBPβ is co-expressed with P-cadherin in breast cancer cells and all the three isoforms function as transcriptional regulators of the CDH3 gene, directly interacting with specific regions of its promoter. Interestingly, this transcriptional activation was only reflected at the P-cadherin protein level concerning the LIP isoform. Taken together, our data show that CDH3 is a newly defined transcriptional target gene of C/EBPβ isoforms in breast cancer, and we also identified the binding sites that are relevant for this activation.
format article
author André Albergaria
Carlos Resende
Ana Rita Nobre
Ana Sofia Ribeiro
Bárbara Sousa
José Carlos Machado
Raquel Seruca
Joana Paredes
Fernando Schmitt
Fernando Schmitt
author_facet André Albergaria
Carlos Resende
Ana Rita Nobre
Ana Sofia Ribeiro
Bárbara Sousa
José Carlos Machado
Raquel Seruca
Joana Paredes
Fernando Schmitt
Fernando Schmitt
author_sort André Albergaria
title CCAAT/enhancer binding protein β (C/EBPβ) isoforms as transcriptional regulators of the pro-invasive CDH3/P-cadherin gene in human breast cancer cells.
title_short CCAAT/enhancer binding protein β (C/EBPβ) isoforms as transcriptional regulators of the pro-invasive CDH3/P-cadherin gene in human breast cancer cells.
title_full CCAAT/enhancer binding protein β (C/EBPβ) isoforms as transcriptional regulators of the pro-invasive CDH3/P-cadherin gene in human breast cancer cells.
title_fullStr CCAAT/enhancer binding protein β (C/EBPβ) isoforms as transcriptional regulators of the pro-invasive CDH3/P-cadherin gene in human breast cancer cells.
title_full_unstemmed CCAAT/enhancer binding protein β (C/EBPβ) isoforms as transcriptional regulators of the pro-invasive CDH3/P-cadherin gene in human breast cancer cells.
title_sort ccaat/enhancer binding protein β (c/ebpβ) isoforms as transcriptional regulators of the pro-invasive cdh3/p-cadherin gene in human breast cancer cells.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/11611a12228544b6af36f2dd13996a77
work_keys_str_mv AT andrealbergaria ccaatenhancerbindingproteinbcebpbisoformsastranscriptionalregulatorsoftheproinvasivecdh3pcadheringeneinhumanbreastcancercells
AT carlosresende ccaatenhancerbindingproteinbcebpbisoformsastranscriptionalregulatorsoftheproinvasivecdh3pcadheringeneinhumanbreastcancercells
AT anaritanobre ccaatenhancerbindingproteinbcebpbisoformsastranscriptionalregulatorsoftheproinvasivecdh3pcadheringeneinhumanbreastcancercells
AT anasofiaribeiro ccaatenhancerbindingproteinbcebpbisoformsastranscriptionalregulatorsoftheproinvasivecdh3pcadheringeneinhumanbreastcancercells
AT barbarasousa ccaatenhancerbindingproteinbcebpbisoformsastranscriptionalregulatorsoftheproinvasivecdh3pcadheringeneinhumanbreastcancercells
AT josecarlosmachado ccaatenhancerbindingproteinbcebpbisoformsastranscriptionalregulatorsoftheproinvasivecdh3pcadheringeneinhumanbreastcancercells
AT raquelseruca ccaatenhancerbindingproteinbcebpbisoformsastranscriptionalregulatorsoftheproinvasivecdh3pcadheringeneinhumanbreastcancercells
AT joanaparedes ccaatenhancerbindingproteinbcebpbisoformsastranscriptionalregulatorsoftheproinvasivecdh3pcadheringeneinhumanbreastcancercells
AT fernandoschmitt ccaatenhancerbindingproteinbcebpbisoformsastranscriptionalregulatorsoftheproinvasivecdh3pcadheringeneinhumanbreastcancercells
AT fernandoschmitt ccaatenhancerbindingproteinbcebpbisoformsastranscriptionalregulatorsoftheproinvasivecdh3pcadheringeneinhumanbreastcancercells
_version_ 1718422649288261632