title: Notch activation stimulates migration of breast cancer cells and promotes tumor growth.
abstract: BACKGROUND
  Dysregulated NOTCH receptor activity has been implicated in breast cancer but the mechanisms by which NOTCH contributes to transformation are not yet clear, as it has context-dependent effects on the properties of transformed cells.
  
  
  METHODS
  We have used various in vitro and in vivo carcinogenic models to analyze the impact of Notch signaling in the onset and progression of breast tumors.
  
  
  RESULTS
  We found that ectopic expression of the Notch1 intracellular domain (N1ICD) in MCF-7 breast adenocarcinoma cell line caused reduction and delocalization of E-CADHERIN levels and increased migratory and invasive abilities. Notch inhibition in the invasive breast cancer cell line MDA-MB-231 resulted in increased E-CADHERIN expression and a parallel reduction in their invasive capacity. The growth of subcutaneous xenografts produced with MCF-7 cells was boosted after N1ICD induction, in a cell autonomous manner. In vivo Notch1 activation in the mammary gland using the MMTV-Cre driver caused the formation of papillary tumors that showed increased Hes1 and Hey1 expression and delocalized E-cadherin staining.
  
  
  CONCLUSIONS
  These results confirm NOTCH1 as a signal triggering epithelial-mesenchymal transition in epithelial cancer cells, which may have implications in tumor dissemination, metastasis and proliferation in vivo. The identification of specific factors interacting with NOTCH signaling could thus be relevant to fully understanding the role of NOTCH in breast neoplasia.
authors.forename: Victoria
authors.initials: V
authors.lastname: Bolós
authors.forename: Emilia
authors.initials: E
authors.lastname: Mira
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martínez-Poveda
authors.forename: Guillermo
authors.initials: G
authors.lastname: Luxán
authors.forename: Marta
authors.initials: M
authors.lastname: Cañamero
authors.forename: Carlos
authors.initials: C
authors.lastname: Martínez-A
authors.forename: Santos
authors.initials: S
authors.lastname: Mañes
authors.forename: José Luis
authors.initials: JL
authors.lastname: de la Pompa
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D051881:Receptor, Notch1 / Q000737:chemistry / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D047368:Tumor Burden
chemical_list: D015820:Cadherins; D051881:Receptor, Notch1; D011960:Receptors, Estrogen; D051880:Receptors, Notch