Specific Inhibition of the Expression of the Promyelocytic Leukemia (PML) Protein by Anti-Sense Oligonucleotides

Document Type: Research Paper

Authors

1 Division of Genetics, Department of Biology, Faculty of Science, Isfahan University, Isfahan, I.R. Iran

2 Department of Laboratory Medicine, MD Anderson Cancer Center, Houston, Texas, USA.

Abstract

In the present study, using anti-sense oligonucleotides the inhibition of expression of the PML protein has
been investigated. The anti-sense oligonucleotides were designed against the translation initiation site of
the PML gene, and their effects were investigated on cellular growth and DNA synthesis. Incubation of normal
human fibroblast cells with the anti-sense oligonucleotides resulted in the complete inhibition of the PML
protein expression. Inhibition of the PML protein expression by anti-sense oligonucleotides was found
to be associated with an increase in cellular growth and doubling time. Furthermore, in cells treated with
the anti-sense oligonucleotides, but not sense or scrambled oligonucleotides (control), the cellular DNA
synthesis also showed a marked increase, confirming the induction of cellular growth upon inhibition of PML
synthesis. These findings clearly demonstrated that the inhibition of the expression of the PML protein could be achieved using the anti-sense oligonucleotides, providing a model for better investigation of the biologic role of PML in the cell.

Keywords