Reduction of erbB2 gene product in mamma carcinoma cell lines by erbB2 mRNA-specific and tyrosine kinase consensus phosphorothioate antisense oligonucleotides.

A considerable reduction of up to 75% at the protein level of the erbB2 gene product was observed using phosphorothioate antisense oligonucleotides directed against specific sequences of the erbB2 mRNA. Antisense oligonucleotides used were the 14-mer (translation start region) and the 17-mer (3' translated region) all-phosphorothioate oligonucleotides (S-ODNs). Sense or random sequences were used as a control. The greatest reduction at the erbB2 protein level was obtained after a 24h incubation with a single dose of 2 microM antisense S-ODN. The erbB2-mRNA-specific and the tyrosine kinase consensus antisense S-ODNs were comparably effective in inhibiting erbB2 expression. Addition of the transfection reagent DOTAP diminished the efficiency of erbB2 protein reduction by antisense S-ODNs after an incubation period of 24h but was more effective after 48h compared to the application of antisense S-ODNs alone.