Arsenite and cadmium promote the development of mammary tumors

Shailaja D. Divekar, Heng Hong Li, Daniela A. Parodi, Tiffany Bita Ghafouri, Renxiang Chen, Kedra Cyrus, Aaron E. Foxworth, Albert J. Fornace, Celia Byrne, Mary Beth Martin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Previous studies demonstrate that the heavy metal cadmium and the metalloid arsenite activate estrogen receptoralpha 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.

Original languageEnglish
Pages (from-to)1005-1014
Number of pages10
JournalCarcinogenesis
Volume41
Issue number7
DOIs
StatePublished - 2021
Externally publishedYes

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