Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells
| العنوان: | Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells |
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| المؤلفون: | Richard J. Santen, Daniel F. Heitjan, Steven J. Santner, Shigeru Masamura |
| المصدر: | The Journal of Clinical Endocrinology & Metabolism. 80:2918-2925 |
| بيانات النشر: | The Endocrine Society, 1995. |
| سنة النشر: | 1995 |
| مصطلحات موضوعية: | medicine.medical_specialty, Polyunsaturated Alkamides, Endocrinology, Diabetes and Metabolism, Transplantation, Heterologous, Clinical Biochemistry, Mammary gland, Mice, Nude, Breast Neoplasms, Biochemistry, Cell Line, Mice, Tissue culture, Endocrinology, Breast cancer, Internal medicine, Tumor Cells, Cultured, medicine, Animals, Humans, Drug Implants, Dose-Response Relationship, Drug, Estradiol, business.industry, Biochemistry (medical), Estrogen Antagonists, Antiestrogen, medicine.disease, medicine.anatomical_structure, Receptors, Estrogen, Cell culture, Cancer cell, Hormonal therapy, Female, business, Cell Division, Hormone |
| الوصف: | Genetic and environmental factors can modulate the level of sensitivity to various hormones, including estrogens. Enhanced sensitivity to estradiol (E2) has been demonstrated in several biological conditions, such as in sheep during the nonbreeding season, in untreated patients with Turner's syndrome, and in the prepubertal state in normal girls. We postulated that secondary responses to hormonal therapy in patients with breast cancer could also result from enhanced E2 sensitivity, developing as an adaptive mechanism to E2 deprivation. The present study used the MCF-7 human breast cancer cell line as a model system to test the concept that enhanced sensitivity to E2 may occur as a result of adaptation to low E2 levels. After depriving MCF-7 cells of estrogens in tissue culture medium for periods of 1-6 months, we established conditions under which replication could be stimulated maximally by 10(-14)-10(-15) mol/L E2. In contrast, wild-type cells not exposed to estrogen deprivation required 10(-10) mol/L E2 to grow at the same rate. Further, the concentration of the antiestrogen, ICI 164384, needed to inhibit growth by 50% in estrogen-deprived cells was much lower than that required in wild-type cells (i.e. 10(-15) vs. 10(-9) mol/L). Nude mice implanted with these estrogen-deprived cells demonstrated an earlier appearance of palpable tumors in response to E2 than animals bearing wild-type cells. Reexposure to 10(-10)-10(-9) mol/L E2, either in vivo or in vitro, returned these cells to the level of estrogen sensitivity observed in wild-type cells. Taken together, these observations suggest that breast cancer cells can adapt to low levels of estrogens by enhancing their sensitivity to E2. |
| تدمد: | 1945-7197 0021-972X |
| DOI: | 10.1210/jcem.80.10.7559875 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4a95d148b88684f2d0523bfa80912faa https://doi.org/10.1210/jcem.80.10.7559875 |
| رقم الانضمام: | edsair.doi.dedup.....4a95d148b88684f2d0523bfa80912faa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19457197 0021972X |
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| DOI: | 10.1210/jcem.80.10.7559875 |