Estrogen receptor beta increases the efficacy of antiestrogens by effects on apoptosis and cell cycling in breast cancer cells
| Autor: | Cathleen D. Valentine, Peter J. Kushner, Leslie Hodges-Gallagher, Suzy El Bader |
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| Rok vydání: | 2007 |
| Předmět: |
endocrine system
Cancer Research medicine.medical_specialty Immunoblotting Estrogen receptor Apoptosis Breast Neoplasms Transfection Estrogen Receptor Modulators Internal medicine Cell Line Tumor polycyclic compounds medicine Estrogen Receptor beta Humans Raloxifene Epidermal growth factor receptor skin and connective tissue diseases Estrogen receptor beta Fulvestrant biology Reverse Transcriptase Polymerase Chain Reaction Cell Cycle Antiestrogen Flow Cytometry Endocrinology Oncology Selective estrogen receptor modulator Cancer research biology.protein Female hormones hormone substitutes and hormone antagonists Tamoxifen medicine.drug HeLa Cells |
| Zdroj: | Breast cancer research and treatment. 109(2) |
| ISSN: | 0167-6806 |
| Popis: | Clinical evidence indicates that higher levels of estrogen receptor beta (ERbeta) predicts improved disease-free and overall survival in patients treated with adjuvant tamoxifen therapy. To better understand the mechanisms in which ERbeta can modulate breast cancer therapies, we introduced ERbeta under an inducible promoter into MCF-7 breast cancer cells. In these cells, induction of ERbeta expression led to a shift in the potency and an increase in the efficacy of tamoxifen to inhibit proliferation. A similar effect on breast cancer cells was observed for two other antiestrogens, raloxifene, and fulvestrant. Induced expression of ERbeta did not enhance the antiproliferative effects of small molecule inhibitors that target the epidermal growth factor receptor, insulin growth factor receptor-1 and histone deacetylase, indicating ERbeta specifically cooperates with antiestrogens. The combination of ERbeta expression, which arrests cells in G2, and tamoxifen, which arrests cells in G1, led to a potent blockade of the cell cycle. ERbeta also increased tamoxifen-induced cell death and cooperated with tamoxifen to induce expression of the pro-apoptotic gene bik. In summary, our data indicates that ERbeta increases the efficacy of antiestrogens by effects on apoptosis and on cell cycling and, together with clinical observations, suggests ERbeta could be a valuable prognostic marker and potential therapeutic target. |
| Databáze: | OpenAIRE |
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