Antisense MBD2 gene therapy inhibits tumorigenesis.
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.
Department of Pharmacology and Therapeutics, McGill University, 3655 Drummond Street, Montreal, PQ H3G 1Y6, Canada.
Andrew
A
Slack
Veronica
V
Bovenzi
Pascal
P
Bigey
M A
MA
Ivanov
Shyam
S
Ramchandani
Sanjoy
S
Bhattacharya
Benjamin
B
tenOever
B
B
Lamrihi
Daniel
D
Scherman
Moshe
M
Szyf
D000256:Adenoviridae; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000628:therapy; D019175:DNA Methylation; D016373:DNA, Antisense / Q000235:genetics / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms; D009374:Neoplasms, Experimental / Q000235:genetics / Q000628:therapy*
D016373:DNA, Antisense; D004268:DNA-Binding Proteins; C115368:MBD2 protein