Article ; Online: The endocrine disruptor cadmium modulates the androgen-estrogen receptors ratio and induces inflammatory cytokines in luminal (A) cell models of breast cancer.
2023 Volume 83, Issue 3, Page(s) 798–809
Abstract: Purpose: Breast cancer (BC) is the most common malignancy that affects women, and it is, to date, their leading cause of death. Luminal A molecular subtype accounts for 40% of BC and is characterized by hormone receptors positive/human epidermal growth ... ...
| Abstract | Purpose: Breast cancer (BC) is the most common malignancy that affects women, and it is, to date, their leading cause of death. Luminal A molecular subtype accounts for 40% of BC and is characterized by hormone receptors positive/human epidermal growth factor 2 expression and current treatment consists of surgery plus aromatase inhibitor therapy. Interestingly, several studies demonstrated that the heavy metal cadmium (Cd), classified as a group 1 human carcinogen and widely spread in the environment, exerts estrogen-like activities in several tissues and suggested an intriguing relationship between increased Cd exposure and BC incidence. Thus, aim of this study was to evaluate effects of Cd on Luminal A BC estrogen receptor (ER) positive/progesterone receptor positive cell models in vitro to characterize the mechanism(s) involved in breast cell homeostasis disruption. Methods: T47D and MCF7 were exposed to Cd (0.5-1 µM) for 6-24 h to evaluate potential alterations in: cells viability, steroid receptors and intracellular signaling by western blot. Moreover, we evaluated the expression of inflammatory cytokines interleukin by RT-PCR. Results: Our results showed a significant induction of androgen receptor (AR) and an increased AR/ER ratio. Further, Cd exposure increased pro-inflammatory cytokines interleukin (IL)6, IL8 and tumor necrosis factor α levels. Finally, as previously demonstrated by our group, Cd alters pathways such as mitogen-activated protein kinase family and protein kinase B. Conclusion: In conclusion, our study demonstrates that Cd modifies the expression and pattern of ERs and AR in BC cell lines, suggesting an alteration of BC cells homeostasis, likely predisposing to a carcinogenetic microenvironment. |
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| MeSH term(s) | Female ; Humans ; Breast Neoplasms/pathology ; Cadmium/toxicity ; Endocrine Disruptors/pharmacology ; Androgens/pharmacology ; Receptors, Androgen/metabolism ; Receptors, Estrogen/metabolism ; Cytokines ; Estrogens ; Interleukin-6 ; Cell Line, Tumor ; Tumor Microenvironment |
| Chemical Substances | Cadmium (00BH33GNGH) ; Endocrine Disruptors ; Androgens ; Receptors, Androgen ; Receptors, Estrogen ; Cytokines ; Estrogens ; Interleukin-6 |
| Language | English |
| Publishing date | 2023-11-18 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 1194484-5 |
| ISSN | 1559-0100 ; 1355-008X ; 0969-711X |
| ISSN (online) | 1559-0100 |
| ISSN | 1355-008X ; 0969-711X |
| DOI | 10.1007/s12020-023-03594-2 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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