Specific inhibition of the expression of the promyelocytic leukemia (PML) protein by anti-sense oligonucleotides

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