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

Breast cancer (BC) is linked to estrogen exposure. Estradiol (E,) 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 PDGFR alpha kinases. Cd increased cell proliferation and the ER-antagonist ICI 182,780 blunted it. To characterize an ER-dependent mechanism, ER alpha/beta expression was evaluated. Cd decreased ER alpha expression, but not ER beta. Cd also increased ERK1/2, Akt and PDGFR alpha 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 PDGFR alpha kinases activity likely by activating c-fos, c-jun and PDGFA by an ER alpha-dependent mechanism. (c) 2006 Elsevier Ireland Ltd. All rights reserved.