Colomer R, Lupu R, Bacus S S, Gelmann E P
Division of Medical Oncology, Vincent T. Lombardi Cancer Research Center, Georgetown University, Washington, DC 20007.
Br J Cancer. 1994 Nov;70(5):819-25. doi: 10.1038/bjc.1994.405.
Amplification and overexpression of the erbB-2 oncogene is an unfavourable prognostic marker in human breast cancer and occurs in approximately 25% of breast carcinomas. We used erbB-2 antisense oligonucleotides to inhibit the proliferation of human breast cancer cell lines. erbB-2 antisense oligonucleotides (20 microM) inhibited the growth and DNA synthesis of breast cancer cell lines with an amplified erbB-2 gene by up to 60%. Control complementary sense oligonucleotides did not inhibit cellular proliferation at the same concentration but showed inhibitory effects at higher concentrations. There was no specific effect of erbB-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-dependent manner. erbB-2 sense oligonucleotides did not decrease the levels of erbB-2 protein. These data indicate that erbB-2 antisense oligonucleotides induce a specific inhibition of erbB-2 protein expression and that erbB-2 gene overexpression is important for the proliferation of the breast cancer cells that have been selected for erbB-2 amplification.
erbB-2癌基因的扩增和过表达是人类乳腺癌中一个不良的预后标志物，约25%的乳腺癌中会出现这种情况。我们使用erbB-2反义寡核苷酸来抑制人乳腺癌细胞系的增殖。erbB-2反义寡核苷酸（20微摩尔）可将erbB-2基因扩增的乳腺癌细胞系的生长和DNA合成抑制高达60%。对照互补有义寡核苷酸在相同浓度下不抑制细胞增殖，但在较高浓度时显示出抑制作用。erbB-2反义寡核苷酸对无erbB-2扩增的乳腺癌细胞系没有特异性作用。通过免疫组织化学测量，erbB-2反义寡核苷酸以剂量依赖的方式降低erbB-2蛋白水平。erbB-2有义寡核苷酸不会降低erbB-2蛋白水平。这些数据表明，erbB-2反义寡核苷酸可特异性抑制erbB-2蛋白表达，且erbB-2基因过表达对于因erbB-2扩增而被选择的乳腺癌细胞的增殖很重要。
