erbB-2 antisense oligonucleotides inhibit the proliferation of breast carcinoma cells with erbB-2 oncogene amplification (original) (raw)

Abstract

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.

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Authors and Affiliations

  1. Division of Medical Oncology, Vincent T. Lombardi Cancer Research Center, Georgetown University, Washington, 20007, DC
    R Colomer

Authors

  1. R Colomer
  2. R Lupu
  3. SS Bacus
  4. EP Gelmann

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Colomer, R., Lupu, R., Bacus, S. et al. _erb_B-2 antisense oligonucleotides inhibit the proliferation of breast carcinoma cells with _erb_B-2 oncogene amplification.Br J Cancer 70, 819–825 (1994). https://doi.org/10.1038/bjc.1994.405

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