title: Transcription factors and molecular epigenetic marks underlying EpCAM overexpression in ovarian cancer.
abstract: BACKGROUND
  The epithelial cell adhesion molecule (EpCAM) is overexpressed on carcinomas, and its downregulation inhibits the oncogenic potential of multiple tumour types. Here, we investigated underlying mechanisms of epcam overexpression in ovarian carcinoma.
  
  
  METHODS
  Expression of EpCAM and DNA methylation (bisulphite sequencing) was determined for ovarian cancer cell lines. The association of histone modifications and 16 transcription factors with the epcam promoter was analysed by chromatin immunoprecipitation. Treatment with 5-Aza-2'-deoxycytidine (5-AZAC) was used to induce EpCAM expression.
  
  
  RESULTS
  Expression of EpCAM was correlated with DNA methylation and histone modifications. Treatment with 5-AZAC induced EpCAM expression in negative cells. Ten transcription factors were associated with the epcam gene in EpCAM expressing cells, but not in EpCAM-negative cells. Methylation of an Sp1 probe inhibited the binding of nuclear extract proteins in electromobility shift assays; such DNA methylation sensitivity was not observed for an NF-κB probe.
  
  
  CONCLUSIONS
  This study provides insights in transcriptional regulation of epcam in ovarian cancer. Epigenetic parameters associated with EpCAM overexpression are potentially reversible, allowing novel strategies for sustained silencing of EpCAM expression.
authors.affiliation: Epigenetic Editing, Department of Pathology and Medical Biology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: B T F
authors.initials: BT
authors.lastname: van der Gun
authors.forename: M L
authors.initials: ML
authors.lastname: de Groote
authors.forename: H G
authors.initials: HG
authors.lastname: Kazemier
authors.forename: A J
authors.initials: AJ
authors.lastname: Arendzen
authors.forename: P
authors.initials: P
authors.lastname: Terpstra
authors.forename: M H J
authors.initials: MH
authors.lastname: Ruiters
authors.forename: P M J
authors.initials: PM
authors.lastname: McLaughlin
authors.forename: M G
authors.initials: MG
authors.lastname: Rots
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000502:physiology; D044127:Epigenesis, Genetic / Q000502:physiology*; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D005819:Genetic Markers; D014157:Transcription Factors