Arsenite and cadmium promote the development of mammary tumors
| Autor: | Daniela A. Parodi, Celia Byrne, Renxiang Chen, Mary Beth Martin, Shailaja D. Divekar, Aaron Foxworth, Tiffany Bita Ghafouri, Kedra Cyrus, Albert J. Fornace, Heng-Hong Li |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.drug_class Arsenites Carcinogenesis AcademicSubjects/MED00710 Mammary gland chemistry.chemical_element Mammary Neoplasms Animal 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Progesterone receptor medicine Benz(a)Anthracenes Animals Humans Cyclin D1 Mammary Glands Human Arsenite Cadmium Estrogen Receptor alpha Estrogens General Medicine Antiestrogen Neoplasm Proteins Rats GREB1 030104 developmental biology medicine.anatomical_structure chemistry Estrogen 030220 oncology & carcinogenesis Cancer research Carcinogens MCF-7 Cells Female Receptors Progesterone Proto-Oncogene Proteins c-fos hormones hormone substitutes and hormone antagonists |
| Zdroj: | Carcinogenesis |
| ISSN: | 1460-2180 |
| Popis: | Previous studies demonstrate that the heavy metal cadmium and the metalloid arsenite activate estrogen receptor-alpha in breast cancer cells by forming a high-affinity complex with the ligand-binding domain of the receptor and that environmentally relevant doses of cadmium have estrogen-like activity in vivo. The present study showed that in estrogen-receptor positive cells, arsenite and cadmium increased the global expression of estrogen-responsive genes and that an environmentally relevant dose of arsenite also had estrogen-like activity in vivo. Similar to estrogens, exposure of ovariectomized animals to arsenite induced the expression of the progesterone receptor, GREB1, and c-fos in the mammary gland and the expression of complement C3, c-fos, and cyclin D1 in the uterus and the increase was blocked by the antiestrogen ICI-182,780. When virgin female animals were fed a diet, that mimics exposure to either arsenite or cadmium, and challenged with the chemical carcinogen dimethylbenzanthracene, there was an increase in the incidence of mammary tumors and a decrease in the time to tumor onset, but no difference in the total number of tumors, tumor multiplicity, or total tumor volume. Together with published results, these data showed that environmentally relevant amounts of arsenite and cadmium had estrogen-like activity in vivo and promoted mammary tumorigenesis. The results suggest that arsenite and cadmium are environmental estrogens that contribute to the risk of developing breast cancer. |
| Databáze: | OpenAIRE |
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