erbB-2 antisense oligonucleotides inhibit the proliferation of breast carcinoma cells with erbB-2 oncogene amplification

R. Colomer, Ruth Lupu, S. S. Bacus, E. P. Gelmann

Research output: Contribution to journalArticle

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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 μM) 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.

Original languageEnglish (US)
Pages (from-to)819-825
Number of pages7
JournalBritish Journal of Cancer
Volume70
Issue number5
StatePublished - 1994
Externally publishedYes

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Antisense Oligonucleotides
Oncogenes
Breast Neoplasms
erbB-2 Genes
Oligonucleotides
Cell Line
Proteins
Immunohistochemistry
Cell Proliferation
DNA
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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erbB-2 antisense oligonucleotides inhibit the proliferation of breast carcinoma cells with erbB-2 oncogene amplification. / Colomer, R.; Lupu, Ruth; Bacus, S. S.; Gelmann, E. P.

In: British Journal of Cancer, Vol. 70, No. 5, 1994, p. 819-825.

Research output: Contribution to journalArticle

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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 μM) 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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N2 - 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 μM) 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.

AB - 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 μM) 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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