CDH4 as a novel putative tumor suppressor gene epigenetically silenced by promoter hypermethylation in nasopharyngeal carcinoma

Cancer Lett. 2011 Oct 1;309(1):54-61. doi: 10.1016/j.canlet.2011.05.016. Epub 2011 Jun 12.

Abstract

We investigated the transcription levels, promoter methylation status and role as a tumor suppressor gene (TSG) of the cadherin CDH4 in nasopharyngeal carcinoma (NPC). The expression of CDH4 was decreased in NPC cell lines, xenografts and primary tumor biopsies. Promoter hypermethylation of CDH4 was detected in all five NPC cell lines, both NPC xenograft lines and 94.3% of primary tumors but not in any of the 12 normal epithelial samples. Loss of CDH4 expression could be restored by the methyltransferase inhibitor 5-aza-2'-deoxycytidine in NPC cell lines. Ectopic expression of CDH4 in the NPC cell lines inhibits cell proliferation, colony formation, migration and elicit cell communication. CDH4 may be a novel putative TSG that can be frequently and tumor-specifically inactivated by its promoter methylation in NPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / genetics*
  • Carcinoma
  • Cell Communication / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • DNA Methylation
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing*
  • Genes, Tumor Suppressor*
  • Humans
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / pathology
  • Neoplasm Transplantation
  • Promoter Regions, Genetic
  • Transcriptional Activation

Substances

  • Cadherins
  • R-cadherin