Antisense MBD2 gene therapy inhibits tumorigenesis

Andrew Slack, Veronica Bovenzi, Pascal Bigey, M. A. Ivanov, Shyam Ramchandani, Sanjoy Bhattacharya, Benjamin tenOever, B. Lamrihi, Daniel Scherman, Moshe Szyf

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Background: Aberration in the pattern of DNA methylation is one of the hallmarks of cancer. We present data suggesting that dysregulation of MBD2, a recently characterized member of a novel family of methylated DNA binding proteins, is involved in tumorigenesis. Two functions were ascribed to MBD2, DNA demethylase activity and repression of methylated genes. Methods: Multiple antisense expression and delivery systems, transfection, electrotransfer and adenoviral were employed to demonstrate that MBD2 is essential in tumorigenesis, both ex vivo and in vivo. Results: Inhibition of MBD2 by antisense expression resulted in inhibition of anchorage-independent growth of antisense transfected cancer cells or cells infected with an adenoviral vector expressing MBD2 antisense. Xenograft tumors treated with an adenoviral vector expressing MBD2 antisense or xenografts treated with electrotransferred plasmids expressing MBD2 antisense showed reduced growth. Conclusions: These results support the hypothesis that one or both of the functions described for MBD2 are critical in tumorigenesis and that MBD2 is a potential anticancer target.

Original languageEnglish (US)
Pages (from-to)381-389
Number of pages9
JournalJournal of Gene Medicine
Volume4
Issue number4
DOIs
StatePublished - Jul 1 2002
Externally publishedYes

Keywords

  • Adenoviral vectors
  • Antisense
  • Demethylase
  • DNA methylation
  • Methylated DNA binding proteins
  • Tumorigenesis

ASJC Scopus subject areas

  • Genetics

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  • Cite this

    Slack, A., Bovenzi, V., Bigey, P., Ivanov, M. A., Ramchandani, S., Bhattacharya, S., tenOever, B., Lamrihi, B., Scherman, D., & Szyf, M. (2002). Antisense MBD2 gene therapy inhibits tumorigenesis. Journal of Gene Medicine, 4(4), 381-389. https://doi.org/10.1002/jgm.288