A genome-wide expression analysis identifies a network of EpCAM-induced cell cycle regulators

K Maaser1, J Borlak

  • 1Molecular Medicine and Medical Biotechnology, Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany.

British Journal of Cancer
|November 13, 2008
PubMed

Insights

EpCAM antibodies increase cancer cell proliferation by affecting cell cycle regulators. Understanding these EpCAM signaling pathways could impact future cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Epithelial cell adhesion molecule (EpCAM) expression is elevated in various carcinomas.
  • EpCAM is a target for tumor diagnosis and EpCAM-based therapies.
  • Intracellular effects and signaling pathways of EpCAM-specific antibodies are largely unknown.

Purpose of the Study:

  • To investigate the intracellular effects of EpCAM-specific antibodies.
  • To identify signaling pathways triggered by EpCAM engagement.
  • To explore the impact of EpCAM antibodies on cancer cell proliferation and gene expression.

Main Methods:

  • Treatment of carcinoma cell lines (A2C12, A549, Caco-2) with a monoclonal EpCAM antibody (G8.8).
  • Assessment of cell proliferation using MTS and 5'-bromo-2'-deoxyuridine (BrdU) labeling assays.
  • Genome-wide gene expression analysis to identify regulated networks and pathways.

Main Results:

  • EpCAM antibody treatment dose-dependently increased proliferation in tested carcinoma cell lines.
  • Genome-wide analysis revealed regulation of cell cycle regulators and other key pathways.
  • Gene expression changes correlated with BrdU labeling data, highlighting impacts on cell cycle, death, growth, and proliferation.

Conclusions:

  • EpCAM is involved in signal transduction, activating intracellular signaling pathways.
  • EpCAM antibody-induced signaling affects critical cellular processes including proliferation and cell cycle.
  • Elucidating EpCAM signaling pathways may necessitate a re-evaluation of current EpCAM-based therapeutic strategies.

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