CCAAT/Enhancer Binding Protein beta (C/EBP beta) Isoforms as Transcriptional Regulators of the Pro-Invasive CDH3/P-Cadherin Gene in Human Breast Cancer Cells

• Tipo: Artigo em Revista Científica Internacional
• Data: 2013

Autores

Albergaria, A (Autor) FMUP; Resende, C (Autor) Outra; Nobre, AR (Autor) Outra; Ribeiro, AS (Autor) Outra; Sousa, B (Autor) Outra; Machado JC (Autor) FMUP; Seruca, R (Autor) FMUP; Joana Paredes (Autor) FMUP; Fernando Schmitt (Autor) FMUP

Revista

Título: PLoS ONE

Vol. 8 Nº 1

Página Final: e55749

ISSN: 1932-6203

Editora: Public Library of Science

Indexação

ISI Web of Knowledge - 18 Citações

Scopus - 19 Citações

Outras Informações

ID Authenticus: P-002-0J7

DOI: 10.1371/journal.pone.0055749

Abstract (EN): 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 beta (C/EBP beta) transcription factor binding sites at the CDH3 promoter, the aim of this study was to assess if the distinct C/EBP beta 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/EBP beta 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/EBPb isoforms in breast cancer, and we also identified the binding sites that are relevant for this activation.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9