title: E47 and Id1 interplay in epithelial-mesenchymal transition.
abstract: E12/E47 proteins (encoded by E2A gene) are members of the class I basic helix-loop-helix (bHLH) transcription factors (also known as E proteins). E47 has been described as repressor of E-cadherin and inducer of epithelial-mesenchymal transition (EMT). We reported previously that EMT mediated by E47 in MDCK cells occurs with a concomitant overexpression of Id1 and Id3 proteins. Id proteins belong to class V of HLH factors that lack the basic domain; they dimerise with E proteins and prevent their DNA interaction, thus, acting as dominant negative of E proteins. Here, we show that E47 interacts with Id1 in E47 overexpressing MDCK cells that underwent a full EMT as well as in mesenchymal breast carcinoma and melanoma cell lines. By conducting chromatin immunoprecipitation assays we demonstrate that E47 binds directly to the endogenous E-cadherin promoter of mesenchymal MDCK-E47 cells in a complex devoid of Id1. Importantly, our data suggest that both E47 and Id1 are required to maintain the mesenchymal phenotype of MDCK-E47 cells. These data support the collaboration between E47 and Id1 in the maintenance of EMT by mechanisms independent of the dominant negative action of Id1 on E47 binding to E-cadherin promoter. Finally, the analysis of several N0 breast tumour series indicates that the expression of E47 and ID1 is significantly associated with the basal-like phenotype supporting the biological significance of the present findings.
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), IdiPAZ, Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Cubillo
authors.forename: Antonio
authors.initials: A
authors.lastname: Diaz-Lopez
authors.forename: Eva P
authors.initials: EP
authors.lastname: Cuevas
authors.forename: Gema
authors.initials: G
authors.lastname: Moreno-Bueno
authors.forename: Hector
authors.initials: H
authors.lastname: Peinado
authors.forename: Amalia
authors.initials: A
authors.lastname: Montes
authors.forename: Vanesa
authors.initials: V
authors.lastname: Santos
authors.forename: Francisco
authors.initials: F
authors.lastname: Portillo
authors.forename: Amparo
authors.initials: A
authors.lastname: Cano
mesh_terms: D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D004285:Dogs; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000502:physiology*; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D008545:Melanoma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010641:Phenotype; D058127:Transcription Factor 3 / Q000502:physiology*
chemical_list: D015820:Cadherins; D051798:Inhibitor of Differentiation Protein 1; D058127:Transcription Factor 3
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