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Bimonte, Viviana M.; Catanzaro, Giuseppina; Po, Agnese; Trocchianesi, Sofia; Besharat, Zein Mersini; Spinello, Zaira; Curreli, Mariaignazia; Fabi, Alessandra; Bei, Roberto; Milella, Michele; Vacca, Alessandra; Ferretti, Elisabetta; Migliaccio, Silvia

The endocrine disruptor cadmium modulates the androgen–estrogen receptors ratio and induces inflammatory cytokines in luminal (A) cell models of breast cancer

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  • Media type: E-Article
  • Title: The endocrine disruptor cadmium modulates the androgen–estrogen receptors ratio and induces inflammatory cytokines in luminal (A) cell models of breast cancer
  • Contributor: Bimonte, Viviana M.; Catanzaro, Giuseppina; Po, Agnese; Trocchianesi, Sofia; Besharat, Zein Mersini; Spinello, Zaira; Curreli, Mariaignazia; Fabi, Alessandra; Bei, Roberto; Milella, Michele; Vacca, Alessandra; Ferretti, Elisabetta; Migliaccio, Silvia
  • imprint: Springer Science and Business Media LLC, 2023
  • Published in: Endocrine
  • Language: English
  • DOI: 10.1007/s12020-023-03594-2
  • ISSN: 1559-0100
  • Keywords: Endocrinology ; Endocrinology, Diabetes and Metabolism
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Purpose</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>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.</jats:p> </jats:sec>