title: Epigenetic control of the basal-like gene expression profile via Interleukin-6 in breast cancer cells.
abstract: BACKGROUND
  Basal-like carcinoma are aggressive breast cancers that frequently carry p53 inactivating mutations, lack estrogen receptor-α (ERα) and express the cancer stem cell markers CD133 and CD44. These tumors also over-express Interleukin 6 (IL-6), a pro-inflammatory cytokine that stimulates the growth of breast cancer stem/progenitor cells.
  
  
  RESULTS
  Here we show that p53 deficiency in breast cancer cells induces a loss of methylation at IL-6 proximal promoter region, which is maintained by an IL-6 autocrine loop. IL-6 also elicits the loss of methylation at the CD133 promoter region 1 and of CD44 proximal promoter, enhancing CD133 and CD44 gene transcription. In parallel, IL-6 induces the methylation of estrogen receptor (ERα) promoter and the loss of ERα mRNA expression. Finally, IL-6 induces the methylation of IL-6 distal promoter and of CD133 promoter region 2, which harbour putative repressor regions.
  
  
  CONCLUSIONS
  We conclude that IL-6, whose methylation-dependent autocrine loop is triggered by the inactivation of p53, induces an epigenetic reprogramming that drives breast carcinoma cells towards a basal-like/stem cell-like gene expression profile.
authors.affiliation: Center for Applied Biomedical Research (CRBA), St, Orsola-Malpighi University Hospital, via Massarenti 9, 40138 Bologna, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: D'Anello
authors.forename: Pasquale
authors.initials: P
authors.lastname: Sansone
authors.forename: Gianluca
authors.initials: G
authors.lastname: Storci
authors.forename: Valentina
authors.initials: V
authors.lastname: Mitrugno
authors.forename: Gabriele
authors.initials: G
authors.lastname: D'Uva
authors.forename: Pasquale
authors.initials: P
authors.lastname: Chieco
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Bonafé
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D047628:Estrogen Receptor alpha; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D015850:Interleukin-6; C000606023:PROM1 protein, human; D010455:Peptides; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53