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.

CONCLUSION:

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: B T F van der Gun, M L de Groote, H G Kazemier, A J Arendzen, P Terpstra, M H J Ruiters, P M J McLaughlin, M G Rots
• Journal: British journal of cancer (Br J Cancer) Vol. 105 Issue 2 Pg. 312-9 (Jul 12 2011) ISSN: 1532-1827 [Electronic] England
• PMID: 21694727 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Biomarkers, Tumor
• Cell Adhesion Molecules
• EPCAM protein, human
• Epithelial Cell Adhesion Molecule
• Genetic Markers
• Transcription Factors

Topics

• Antigens, Neoplasm (genetics, metabolism)
• Base Sequence
• Biomarkers, Tumor (genetics, metabolism)
• Carcinoma (genetics, metabolism)
• Cell Adhesion Molecules (genetics, metabolism)
• Cell Line, Tumor
• DNA Methylation (physiology)
• Epigenesis, Genetic (physiology)
• Epithelial Cell Adhesion Molecule
• Female
• Gene Expression Regulation, Neoplastic
• Genetic Markers (physiology)
• Humans
• Models, Biological
• Molecular Sequence Data
• Ovarian Neoplasms (genetics, metabolism)
• Transcription Factors (genetics, metabolism, physiology)
• Up-Regulation (genetics)