title: Bidirectional modulation of endogenous EpCAM expression to unravel its function in ovarian cancer.
abstract: BACKGROUND
  The epithelial cell adhesion molecule (EpCAM) is overexpressed on most carcinomas. Dependent on the tumour type, its overexpression is either associated with improved or worse patient survival. For ovarian cancer, however, the role of EpCAM remains unclear.
  
  
  METHODS
  Cell survival of ovarian cancer cell lines was studied after induction or repression of endogenous EpCAM expression using siRNA/cDNA or artificial transcription factors (ATF) consisting of engineered zinc-fingers fused to either a transcriptional activator or repressor domain.
  
  
  RESULTS
  Two ATFs were selected as the most potent down- and upregulator, showing at least a two-fold alteration of EpCAM protein expression compared with control. Downregulation of EpCAM expression resulted in growth inhibition in breast cancer, but showed no effect on cell growth in ovarian cancer. Induction or further upregulation of EpCAM expression decreased ovarian cancer cell survival.
  
  
  CONCLUSIONS
  The bidirectional ATF-based approach is uniquely suited to study cell-type-specific biological effects of EpCAM expression. Using this approach, the oncogenic function of EpCAM in breast cancer was confirmed. Despite its value as a diagnostic marker and for immunotherapy, EpCAM does not seem to represent a therapeutic target for gene expression silencing in ovarian cancer.
authors: Epigenetic Editing, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen 9713 GZ, The Netherlands.
authors: B T F
authors: BT
authors: van der Gun
authors: C
authors: C
authors: Huisman
authors: S
authors: S
authors: Stolzenburg
authors: H G
authors: HG
authors: Kazemier
authors: M H J
authors: MH
authors: Ruiters
authors: P
authors: P
authors: Blancafort
authors: M G
authors: MG
authors: Rots
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D015536:Down-Regulation; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015533:Transcriptional Activation; D015854:Up-Regulation; D016335:Zinc Fingers
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D034741:RNA, Small Interfering
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