title: Cell identity disruption in breast cancer precursors.
abstract: BACKGROUND
  Mammary epithelial cell identity depends on a set of genes epigenetically-regulated by maintenance proteins, the best-characterized of which belong to the Trithorax and Polycomb groups. Perturbations in expression of these proteins may disrupt cell identity and trigger tumor initiation.
  
  
  METHODS
  The pattern of expression of a panel of genes involved in control of cell identity and mammary gland remodeling was investigated in two precancerous lesions, atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) and compared to the corresponding histologically normal tissue.
  
  
  RESULTS
  ADH and DCIS showed a close association in overexpression of Polycomb complex components, silencing of Homeobox A (HOXA) cluster gene, and overexpression of the genes involved in estrogen signaling, specifically, forkhead box A1 (FOXA1) and GATA binding protein 3 (GATA3) pioneer factors, and estrogen receptor-1 (ESR1).
  
  
  CONCLUSIONS
  Our findings support the hypothesis that disruption of epigenetic control is associated with loss of cell identity and acquisition of a constitutive estrogen-dependent terminally-differentiated luminal phenotype.
authors.affiliation: Department of Clinical and Community Health Sciences, Medical Statistics, Biometry and Bioinformatics, University of Milan, Via Vanzetti 5, 20133, Milan, Italy. danila.coradini@yahoo.it.
authors.forename: Danila
authors.initials: D
authors.lastname: Coradini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Boracchi
authors.forename: Saro
authors.initials: S
authors.lastname: Oriana
authors.forename: Elia
authors.initials: E
authors.lastname: Biganzoli
authors.forename: Federico
authors.initials: F
authors.lastname: Ambrogi
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: Mammary epithelium; atypical ductal hyperplasia; cell identity; ductal carcinoma in situ