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Activation of the Her2/neu receptor leads to antiestrogen resistance, but acquired resistance is not caused by altered ErbB expression and activation

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Development of acquired resistance against antiestrogen treatment is a serious problem in human breast cancer, and knowledge of alterations resulting in resistance is important for selection of further treatment. To mimic the clinical situation we have established a series of MCF-7 human breast cancer cell lines by long term treatment with the antiestrogens tamoxifen, ICI 164,384, and ICI 182,780 (Faslodex). Common for these cell lines is a decreased expression of the estrogen receptor α (ERα). In human breast cancer, lack of response to endocrine therapy is often associated with decreased expression of the estrogen receptor and increased expression of epidermal growth factor receptor (EGFR) and/or HER-2/neu (ErbB-2). Our antiestrogen-resistant cell lines did not express altered levels of EGFR, HER-2/neu, ErbB-3 and ErbB-4. Estrogen and antiestrogen regulation of HER-2/neu expression was essentially similar in parent and resistant MCF-7 cells. Treatment with antibodies to HER-2/neu (Herceptin) did not affect growth of MCF-7 cells or resistant cells, indicating that in this in vitro model system, acquired antiestrogen resistance does not emerge from activation of the HER-2/neu signalling pathway. However, addition of heregulin1-β 1 abolished the inhibitory activity of ICI 182,780 on MCF-7 cells, demonstrating that activation of the HER-2/neu receptor signalling pathway can override the growth inhibitory effect of ICI 182,780. The effect of heregulin1-β 1 could be abrogated by Herceptin.

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Larsen, S., Lykkesfeldt, A. Activation of the Her2/neu receptor leads to antiestrogen resistance, but acquired resistance is not caused by altered ErbB expression and activation. Breast Cancer Res 2, P3.03 (2000). https://doi.org/10.1186/bcr156

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  • DOI: https://doi.org/10.1186/bcr156

Keywords

  • Epidermal Growth Factor Receptor
  • Tamoxifen
  • Human Breast Cancer
  • Human Breast Cancer Cell Line
  • Herceptin