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

• Published in: PloS one Vol. 7; no. 9; p. e45970
• Main Authors: Li, Jie, Mo, Minli, Chen, Zhao, Chen, Zhe, Sheng, Qing, Mu, Hang, Zhang, Fang, Zhang, Yi, Zhi, Xiu-Yi, Li, Hui, He, Biao, Zhou, Hai-Meng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.09.2012; Public Library of Science (PLoS)
• Subjects: Adenoviridae - genetics; Animals; Biology; Cancer; Carcinogenesis; Carcinogens; Cell growth; Cell Line, Tumor; Cell lines; Cell Proliferation; Deoxyribonucleic acid; DNA; DNA methylation; Drosophila; Education; Embryogenesis; Embryonic growth stage; Emx2 gene; Endometrial cancer; Ethics; Female; Fruit flies; Gastric cancer; Gene expression; Gene Expression Regulation, Neoplastic; Gene therapy; Genetic Therapy; Genetic Vectors - genetics; Genetic Vectors - therapeutic use; Genomes; Genomics; Homeobox; Homeodomain Proteins - genetics; Hospitals; Humans; Laboratories; Life sciences; Lung cancer; Medicine; Mice; Mice, Inbred BALB C; Mutation; Proteins; Signal transduction; Signaling; Spiracles; Stomach - metabolism; Stomach - pathology; Stomach cancer; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Stomach Neoplasms - therapy; Transcription Factors - genetics; Tumor cell lines; Tumor suppressor genes; Tumorigenesis; Tumors; Up-Regulation; Vectors (Biology); Wnt protein; Wnt Signaling Pathway; Xenografts; Beijing China; San Francisco California; California; United States > US; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0045970

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. 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. 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.