title: Two possible mechanisms of epithelial to mesenchymal transition in invasive ductal breast cancer.
abstract: Epithelial to mesenchymal transition (EMT) occurs in embryogenesis and normal development. It has been predominantly described in vitro and in animal studies, but EMT is also implicated in the progression of many cancers with proposed roles in invasion, metastasis and resistance to treatment. It is closely associated with loss of epithelial-specific protein expression and up-regulation of mesenchymal proteins, but several pathways are implicated in its execution. We explored what are the expression patterns of EMT proteins in human breast cancer. We interrogated two independent cohorts enriched for high-grade, invasive, ductal breast cancers. We used quantitative immunofluorescence to study the expression of key EMT proteins. Statistical associations to define protein profiles were based on Pearson's correlations. E-cadherin down-regulation in breast cancer was associated with β-catenin down-regulation, but not with up-regulation of mesenchymal markers. While EMT-related transcription repressors were expressed in some breast cancers, their expression did not negatively correlate with E-cadherin. Instead, an additional EMT profile was identified, composing Snail and Slug. In conclusion, EMT occurs in human breast cancer in a manner distinct to that seen in vitro. Certain EMT events are uncoupled from E-cadherin down-regulation and may constitute a novel EMT profile, which warrants further exploration.
authors.affiliation: Breakthrough Breast Cancer Research Unit and Division of Pathology, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dubois-Marshall
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Thomas
authors.forename: Dana
authors.initials: D
authors.lastname: Faratian
authors.forename: David J
authors.initials: DJ
authors.lastname: Harrison
authors.forename: Elad
authors.initials: E
authors.lastname: Katz
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C050361:CDH2 protein, human; D015820:Cadherins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051176:beta Catenin