ERBB-2 ANTISENSE OLIGONUCLEOTIDES INHIBIT THE PROLIFERATION OF BREAST-CARCINOMA CELLS WITH ERBB-2 ONCOGENE AMPLIFICATION

Amplification and overexpression of the erbB-2 oncogene is an unfavour able prognostic marker in human breast cancer and occurs in approximat ely 25% of breast carcinomas. We used erbB-2 antisense oligonucleotide s to inhibit the proliferation of human breast cancer cell lines. erbB -2 antisense oligonucleotides (20 mu M) inhibited the growth and DNA s ynthesis of breast cancer cell lines with an amplified erbB-2 gene by up to 60%. Control complementary sense oligonucleotides did not inhibi t cellular proliferation at the same concentration but showed inhibito ry effects at higher concentrations. There was no specific effect of e rbB-2 antisense oligonucleotides on breast cancer cell lines that had no amplification of erbB-2. erbB-2 antisense oligonucleotides reduced erbB-2 protein levels, measured by immunohistochemistry, in a dose-dep endent manner. erbB-2 sense oligonucleotides did not decrease the leve ls of erbB-2 protein. These data indicate that erbB-2 antisense oligon ucleotides induce a specific inhibition of erbB-2 protein expression a nd that erbB-2 gene overexpression is important for the proliferation of the breast cancer cells that have been selected for erbB-2 amplific ation.