Adenoviral delivery of the EMX2 gene suppresses growth in human gastric cancer

PLoS One. 2012;7(9):e45970. doi: 10.1371/journal.pone.0045970. Epub 2012 Sep 21.

Abstract

Background: EMX2 is a human orthologue of the Drosophila empty spiracles homeobox gene that has been implicated in embryogenesis. Recent studies suggest possible involvement of EMX2 in human cancers; however, the role of EMX2 in carcinogenesis needs further exploration.

Results: In this study, we reported that down-regulation of EMX2 expression was significantly correlated with EMX2 promoter hypermethylation in gastric cancer. Restoring EMX2 expression using an adenovirus delivery system in gastric cancer cell lines lacking endogenous EMX2 expression led to inhibition of cell proliferation and Wnt signaling pathway both in vitro and in a gastric cancer xenograft model in vivo. In addition, we observed that animals treated with the adenoviral EMX2 expression vector had significantly better survival than those treated with empty adenoviral vector.

Conclusion: Our study suggests that EMX2 is a putative tumor suppressor in human gastric cancer. The adenoviral-EMX2 may have potential as a novel gene therapy for the treatment of patients with gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gastric Mucosa / metabolism
  • Gene Expression Regulation, Neoplastic
  • Genetic Therapy
  • Genetic Vectors / genetics
  • Genetic Vectors / therapeutic use*
  • Homeodomain Proteins / genetics*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Stomach / pathology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*
  • Transcription Factors / genetics*
  • Up-Regulation
  • Wnt Signaling Pathway

Substances

  • Homeodomain Proteins
  • Transcription Factors
  • empty spiracles homeobox proteins

Grants and funding

This work was supported by funds from the National Key Basic Research and Development (973) Program of China (2011CB910800 and 2012CB917304), the National Natural Science Foundation of China (31170732), the Natural Science Foundation of Zhejiang Province (Y2101329), and the Postdoctoral Science Foundation of Zhejiang Province (2010-BSH-031). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.