Cadmium induces mitogenic signaling in breast cancer cell by an ERalpha-dependent mechanism.
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Brama M, Gnessi L, Basciani S, Cerulli N, Politi L, Spera G, Mariani S, Cherubini S, Scotto d'Abusco A, Scandurra R, Migliaccio S
Cadmium induces mitogenic signaling in breast cancer cell by an ERalpha-dependent mechanism.
Mol Cell Endocrinol. 2007 Jan 29;264(1-2):102-8. Epub 2006 Nov 27.
- PubMed ID
- 17125913 [ View in PubMed]
- Abstract
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 PDGFRalpha kinases. Cd increased cell proliferation and the ER-antagonist ICI 182,780 blunted it. To characterize an ER-dependent mechanism, ERalpha/beta expression was evaluated. Cd decreased ERalpha expression, but not ERbeta. Cd also increased ERK1/2, Akt and PDGFRalpha 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 PDGFRalpha kinases activity likely by activating c-fos, c-jun and PDGFA by an ERalpha-dependent mechanism.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Estradiol Estrogen receptor alpha Protein Humans YesAgonistDetails Estradiol acetate Estrogen receptor alpha Protein Humans YesAgonistDetails Estradiol benzoate Estrogen receptor alpha Protein Humans YesAgonistDetails Estradiol cypionate Estrogen receptor alpha Protein Humans YesAgonistDetails Estradiol dienanthate Estrogen receptor alpha Protein Humans YesAgonistDetails Estradiol valerate Estrogen receptor alpha Protein Humans YesAgonistDetails Estrone sulfate Estrogen receptor alpha Protein Humans YesAgonistDetails Ethinylestradiol Estrogen receptor alpha Protein Humans YesAgonistDetails