Affiliation:
1. Department of Oncology, Georgetown University, Washington DC, USA
2. Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington DC, USA
3. Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
Abstract
AbstractPrevious 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.
Funder
National Institutes of Health
American Institute for Cancer Research
Department of Defense
Howard Hughes Medical Institute
Gewirz Foundation
Uniformed Services University of the Health Sciences
Publisher
Oxford University Press (OUP)
Subject
Cancer Research,General Medicine
Cited by
18 articles.
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