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.
abstract: 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.
authors: Cancer Genetics Group, Institute of Molecular Pathology and Immunology of Porto University (IPATIMUP), Porto, Portugal.
authors: André
authors: A
authors: Albergaria
authors: Carlos
authors: C
authors: Resende
authors: Ana Rita
authors: AR
authors: Nobre
authors: Ana Sofia
authors: AS
authors: Ribeiro
authors: Bárbara
authors: B
authors: Sousa
authors: José Carlos
authors: JC
authors: Machado
authors: Raquel
authors: R
authors: Seruca
authors: Joana
authors: J
authors: Paredes
authors: Fernando
authors: F
authors: Schmitt
mesh_terms: D001665:Binding Sites; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020033:Protein Isoforms; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; C512197:CDH3 protein, human; D015820:Cadherins; D020033:Protein Isoforms; D008156:Luciferases