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

Abstract

In the present study, using anti-sense oligonucleotides the inhibition of expression of the PML protein has<br />been investigated. The anti-sense oligonucleotides were designed against the translation initiation site of<br />the PML gene, and their effects were investigated on cellular growth and DNA synthesis. Incubation of normal<br />human fibroblast cells with the anti-sense oligonucleotides resulted in the complete inhibition of the PML<br />protein expression. Inhibition of the PML protein expression by anti-sense oligonucleotides was found<br />to be associated with an increase in cellular growth and doubling time. Furthermore, in cells treated with<br />the anti-sense oligonucleotides, but not sense or scrambled oligonucleotides (control), the cellular DNA<br />synthesis also showed a marked increase, confirming the induction of cellular growth upon inhibition of PML<br />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.<br /><br />