title: Snail and slug play distinct roles during breast carcinoma progression.
abstract: OBJECTIVE
  Carcinoma progression is linked to a partially dedifferentiated epithelial cell phenotype. As previously suggested, this regulation could involve transcription factors, Snail and Slug, known to promote epithelial-mesenchymal transitions during development. Here, we investigate the role of Snail and Slug in human breast cancer progression.
  
  
  METHODS
  We analyzed Snail, Slug, and E-cadherin RNA expression levels and protein localization in large numbers of transformed cell lines and breast carcinomas, examined the correlation with tumor histologic features, and described, at the cellular level, Snail and Slug localization in carcinomas using combined in situ hybridization and immunolocalization.
  
  
  RESULTS
  In contrast with transformed cell lines, Slug was found to colocalize with E-cadherin at the cellular level in normal mammary epithelial cells and all tested carcinomas. Snail also colocalized at the cellular level with E-cadherin in tumors expressing high levels of Snail RNA. In addition, Snail was significantly expressed in tumor stroma, varying with tumors. Slug and Snail genes were significantly overexpressed in tumors associated with lymph node metastasis. Finally, the presence of semidifferentiated tubules within ductal carcinomas was linked to Slug expression levels similar to or above normal breast samples.
  
  
  CONCLUSIONS
  These results suggest that Snail or Slug expression in carcinoma cells does not generally preclude significant E-cadherin expression. They emphasize a link between Snail, Slug, and lymph node metastasis in a large sampling of mammary carcinomas, and suggest a role for Slug in the maintenance of semidifferentiated structures. Snail and Slug proteins seem to support distinct tumor invasion modes and could provide new therapeutic targets.
authors.affiliation: EMI229 Institut National de la Sante et de la Recherche Medicale, Genotypes et Phenotypes Tumoraux, Centre de Recherche en Cancerologie, CRLC Val d'Aurelle-Paul Lamarque, Montpellier, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Côme
authors.forename: Fabrice
authors.initials: F
authors.lastname: Magnino
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bibeau
authors.forename: Pascal
authors.initials: P
authors.lastname: De Santa Barbara
authors.forename: Karl Friedrich
authors.initials: KF
authors.lastname: Becker
authors.forename: Charles
authors.initials: C
authors.lastname: Theillet
authors.forename: Pierre
authors.initials: P
authors.lastname: Savagner
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D015820:Cadherins / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D015870:Gene Expression; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010641:Phenotype; D000071250:Snail Family Transcription Factors; D013223:Statistics as Topic; D017154:Stromal Cells / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000378:metabolism
chemical_list: D015820:Cadherins; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014746:Vimentin