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Antisense MBD2 gene therapy inhibits tumorigenesis
Author(s) -
Slack Andrew,
Bovenzi Veronica,
Bigey Pascal,
Ivanov M. A.,
Ramchandani Shyam,
Bhattacharya Sanjoy,
tenOever Benjamin,
Lamrihi B.,
Scherman Daniel,
Szyf Moshe
Publication year - 2002
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.288
Subject(s) - carcinogenesis , transfection , demethylase , sense (electronics) , biology , dna methylation , cancer research , microbiology and biotechnology , antisense rna , genetic enhancement , viral vector , vectors in gene therapy , gene , gene expression , chemistry , epigenetics , genetics , recombinant dna
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. Copyright © 2002 John Wiley & Sons, Ltd.