title: Transcriptome analysis of Wnt3a-treated triple-negative breast cancer cells.
abstract: The canonical Wnt/β-catenin pathway is activated in triple-negative breast cancer (TNBC). The activation of this pathway leads to the expression of specific target genes depending on the cell/tissue context. Here, we analyzed the transcriptome of two different TNBC cell lines to define a comprehensive list of Wnt target genes. The treatment of cells with Wnt3a for 6h up-regulated the expression (fold change > 1.3) of 59 genes in MDA-MB-468 cells and 241 genes in HCC38 cells. Thirty genes were common to both cell lines. Beta-catenin may also be a transcriptional repressor and we found that 18 and 166 genes were down-regulated in response to Wnt3a treatment for 6h in MDA-MB-468 and HCC38 cells, respectively, of which six were common to both cell lines. Only half of the activated and the repressed transcripts have been previously described as Wnt target genes. Therefore, our study reveals 137 novel genes that may be positively regulated by Wnt3a and 104 novel genes that may be negatively regulated by Wnt3a. These genes are involved in the Wnt pathway itself, and also in TGFβ, p53 and Hedgehog pathways. Thorough characterization of these novel potential Wnt target genes may reveal new regulators of the canonical Wnt pathway. The comparison of our list of Wnt target genes with those published in other cellular contexts confirms the notion that Wnt target genes are tissue-, cell line- and treatment-specific. Genes up-regulated in Wnt3a-stimulated cell lines were more strongly expressed in TNBC than in luminal A breast cancer samples. These genes were also overexpressed, but to a much lesser extent, in HER2+ and luminal B tumors. We identified 72 Wnt target genes higher expressed in TNBCs (17 with a fold change >1.3) which may reflect the chronic activation of the canonical Wnt pathway that occurs in TNBC tumors.
authors.affiliation: Breast Cancer Biology Group, Translational Research Department, Institut Curie, Centre de Recherche, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Maubant
authors.affiliation: Breast Cancer Biology Group, Translational Research Department, Institut Curie, Centre de Recherche, Paris, France; INSERM U900, Bioinformatics, Biostatistics, Epidemiology and Computational Systems Biology of Cancer, Institut Curie, Centre de Recherche, Paris, France; Mines ParisTech, Fontainebleau, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Tesson
authors.affiliation: Breast Cancer Biology Group, Translational Research Department, Institut Curie, Centre de Recherche, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Maire
authors.affiliation: Breast Cancer Biology Group, Translational Research Department, Institut Curie, Centre de Recherche, Paris, France.
authors.forename: Mengliang
authors.initials: M
authors.lastname: Ye
authors.affiliation: Unité de Recherche en Génomique Végétale, INRA-CNRS-Université d'Evry Val d'Essonne, Evry, France.
authors.forename: Guillem
authors.initials: G
authors.lastname: Rigaill
authors.affiliation: Platform of Molecular Biology Facilities, Translational Research Department, Institut Curie, Centre de Recherche, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Gentien
authors.affiliation: Institut de Recherches SERVIER, Pôle Innovation Thérapeutique Oncologie, Croissy-sur-Seine, France.
authors.forename: Francisco
authors.initials: F
authors.lastname: Cruzalegui
authors.affiliation: Institut de Recherches SERVIER, Pôle Innovation Thérapeutique Oncologie, Croissy-sur-Seine, France.
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Tucker
authors.affiliation: Translational Research Department, Institut Curie, Centre de Recherche, Paris, France.
authors.forename: Sergio
authors.initials: S
authors.lastname: Roman-Roman
authors.affiliation: Breast Cancer Biology Group, Translational Research Department, Institut Curie, Centre de Recherche, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Dubois
mesh_terms: D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D006801:Humans; D015533:Transcriptional Activation / Q000187:drug effects; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D060449:Wnt Signaling Pathway / Q000187:drug effects; D060509:Wnt3A Protein / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D060509:Wnt3A Protein
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