Acquired antiestrogen resistance in MCF-7 human breast cancer sublines is not accomplished by altered expression of receptors in the ErbB-family

Larsen, S. S., Egeblad, M., Jaattela, M., Lykkesfeldt, A. E. (November 1999) Acquired antiestrogen resistance in MCF-7 human breast cancer sublines is not accomplished by altered expression of receptors in the ErbB-family. Breast cancer research and treatment, 58 (1). pp. 41-56. ISSN 0167-6806 (Print)0167-6806

DOI: 10.1023/A:1006232830161


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. Common for these cell lines is a decreased expression of the estrogen receptor alpha (ER alpha). 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, or 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 signaling pathway. In MCF-7 cells transfected with HER-2/neu and/or ErbB-3, overexpression alone did not result in resistance. However, addition of heregulinl-beta1 abolished the inhibitory activity of ICI 182,780 on both vector and HER-2/neu/ErbB-3 transfected MCF-7 cells, demonstrating that activation of the HER-2/neu receptor signaling pathway can override the growth inhibitory effect of ICI 182,780.

Item Type: Paper
Uncontrolled Keywords: Blotting, Northern Blotting, Western Breast Neoplasms/genetics/*metabolism DNA Primers Drug Resistance, Neoplasm Enzyme-Linked Immunosorbent Assay Estradiol/analogs & derivatives/pharmacology Estrogen Antagonists/*pharmacology Female Gene Expression Regulation, Neoplastic Humans Polyunsaturated Alkamides Receptor, erbB-2/*metabolism Reverse Transcriptase Polymerase Chain Reaction Tamoxifen/pharmacology Tumor Cells, Cultured/drug effects
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > ErbB
diseases & disorders > cancer > cancer types > breast cancer
CSHL Authors:
Communities: CSHL labs > Egeblad lab
Depositing User: Matt Covey
Date: November 1999
Date Deposited: 05 Dec 2014 14:43
Last Modified: 05 Dec 2014 14:43
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