Cyclin D1 expression is dependent on estrogen receptor function in tamoxifen-resistant breast cancer cells
| Autor: | Michael W. Hartl, Tina M. Rutherford, Robin L. Kilker, Maricarmen D. Planas-Silva |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism Cyclin D Clinical Biochemistry Cyclin B Estrogen receptor Breast Neoplasms Biochemistry Endocrinology Cyclin D1 Internal medicine Cell Line Tumor medicine Humans skin and connective tissue diseases Molecular Biology Estrogen receptor beta biology Cell Cycle Cell Biology Antiestrogen Gene Expression Regulation Neoplastic Tamoxifen Receptors Estrogen Drug Resistance Neoplasm biology.protein Cancer research Molecular Medicine Female Estrogen receptor alpha hormones hormone substitutes and hormone antagonists Cell Division medicine.drug |
| Zdroj: | The Journal of steroid biochemistry and molecular biology. 92(1-2) |
| ISSN: | 0960-0760 |
| Popis: | The development of resistance to tamoxifen, the most common antiestrogen used in the treatment of breast cancer, is a frequent and severe clinical problem. Tamoxifen-resistant tumors are still capable of responding to other hormonal therapies such as those that downregulate estrogen receptor expression. Mechanisms leading to acquisition of tamoxifen-resistant but hormone-sensitive growth are not completely understood. In tamoxifen-sensitive breast cancer cells, tamoxifen inhibits, whereas estrogen induces, expression of cyclin D1, a key cell cycle regulatory protein. Ectopic expression of cyclin D1 can lead to antiestrogen resistance. Thus, to determine whether cyclin D1 is involved in the growth of tamoxifen-resistant cells, we developed several tamoxifen-resistant variants from MCF-7 cells. These variants grow in the absence of estrogen or in the presence of tamoxifen, but their growth is inhibited by estrogen receptor downregulators. We show here that cyclin D1 expression is maintained at comparable levels in all tamoxifen-resistant variants, whereas pS2, another estrogen-regulated protein, is not. The addition of physiological levels of estrogen further stimulates cyclin D1 expression and proliferation. In contrast, treatment with estrogen receptor downregulators decreases cyclin D1 expression and proliferation. Thus, changes in cyclin D1 expression upon second-line hormonal therapy may predict hormonal sensitivity of tamoxifen-resistant tumors. These studies suggest that estrogen receptor mediates cyclin D1 expression and growth of tamoxifen-resistant tumors. |
| Databáze: | OpenAIRE |
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