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...
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doaj-11611a12228544b6af36f2dd13996a772021-03-03T23:45:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5574910.1371/journal.pone.0055749CCAAT/enhancer binding protein β (C/EBPβ) isoforms as transcriptional regulators of the pro-invasive CDH3/P-cadherin gene in human breast cancer cells.André AlbergariaCarlos ResendeAna Rita NobreAna Sofia RibeiroBárbara SousaJosé Carlos MachadoRaquel SerucaJoana ParedesFernando SchmittFernando SchmittP-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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23405208/?tool=EBI |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
André Albergaria Carlos Resende Ana Rita Nobre Ana Sofia Ribeiro Bárbara Sousa José Carlos Machado Raquel Seruca Joana Paredes Fernando Schmitt Fernando Schmitt |
spellingShingle |
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. PLoS ONE |
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) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
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. |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23405208/?tool=EBI |
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