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Bidirectional modulation of endogenous EpCAM expression to unravel its function in ovarian cancer

van der Gun, B. T. F., Huisman, C., Stolzenburg, S., Kazemier, H. G., Ruiters, M. H. J., Blancafort, P. & Rots, M. G., 5-Mar-2013, In : British Jounal of Cancer. 108, 4, p. 881-886 6 p.

Research output: Contribution to journalArticleAcademicpeer-review

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.

Conclusion: 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.

Original languageEnglish
Pages (from-to)881-886
Number of pages6
JournalBritish Jounal of Cancer
Volume108
Issue number4
Publication statusPublished - 5-Mar-2013

    Keywords

  • EpCAM, ATFs, ovarian cancer, zinc-fingers, BREAST-CANCER, EP-CAM, TRANSCRIPTION FACTORS, POOR-PROGNOSIS, OVEREXPRESSION, CELLS, CONTRIBUTES, CARCINOMA, INVASION, MARKER

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