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Cadmium induces mitogenic signaling in breast cancer cell by an ERα-dependent mechanism *


Breast cancer (BC) is linked to estrogen exposure. Estradiol (E2) stimulates BC cells proliferation by binding the estrogen receptor (ER). Hormone-related cancers have been linked to estrogenic environmental contaminants. Cadmium (Cd) a toxic pollutant, acts as estrogens in BC cells. Purpose of our study was to evaluate whether Cd regulates MCF-7 cell proliferation by activating ERK1/2, Akt and PDGFRα kinases. Cd increased cell proliferation and the ER-antagonist ICI 182,780 blunted it. To characterize an ER-dependent mechanism, ERα/β expression was evaluated. Cd decreased ERα expression, but not ERβ. Cd also increased ERK1/2, Akt and PDGFRα phosphorylation while ICI blocked it. Since stimulation of phosphorylation was slower than expected, c-fos and c-jun proto-oncogenes, and PDGFA were analyzed. Cd rapidly increased c-jun, c-fos and PDGFA expression. Cells were also co-incubated with the Cd and specific kinases inhibitors, which blocked the Cd-stimulated proliferation.

In conclusion, our results indicate that Cd increases BC cell proliferation in vitro by stimulating Akt, ERK1/2 and PDGFRα kinases activity likely by activating c-fos, c-jun and PDGFA by an ERα-dependent mechanism.


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As with any procedure, there could be pain or other substantial risks involved. These concerns should be discussed with your health care provider prior to any treatment so that you have proper informed consent and understand that there are no guarantees to healing.

THE INFORMATION IN THIS WEBSITE IS OFFERED FOR GENERAL EDUCATIONAL PURPOSES ONLY AND DOES NOT IMPLY OR GIVE MEDICAL ADVICE. No Doctor/Patient relationship shall be deemed to have arisen simply by reading the information contained on these pages, and you should consult with your personal physician/care giver regarding your medical treatment before undergoing any sort of treatment or therapy.

Published on 01-19-2010
Authors: Marina Bramaa, Lucio Gnessib, Sabrina Bascianib, Nicola Cerullic, Laura Politia, Giovanni Sperab, Stefania Marianib, Sara Cherubinib, Anna Scotto d.Abuscoa, Roberto Scandurraa and Silvia Migliaccio
Source: Molecular and Cellular Endocrinology, Volume 264, Issues 1-2, 29 January 2007, Pages 102-108