Cadmium induces mitogenic signaling in breast cancer cell by an ERα-dependent mechanism
Cadmium induces mitogenic signaling in breast cancer cell by an ERα-dependent mechanism
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DOI：
10.1016/j.mce.2006.10.013
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发表时间：
2007-01-29
影响因子：
4.1
通讯作者：
Migliaccio, Silvia
中科院分区：
文献类型：
--
作者：
Brama, Marina;Gnessi, Lucio;Migliaccio, Silvia
乳腺癌（BC）与雌激素暴露有关。雌二醇（Estradiol， E,）通过结合雌激素受体（ER）刺激BC细胞增殖。激素相关的癌症与雌激素环境污染物有关。镉（Cd）是一种有毒污染物，在BC细胞中起雌激素的作用。我们的研究目的是评估Cd是否通过激活ERK1/2、Akt和PDGFR α激酶来调节MCF-7细胞的增殖。Cd增加细胞增殖，而内质拮抗剂ICI 182780则使细胞增殖减弱。为了表征内质网依赖机制，我们评估了内质网α / β的表达。Cd降低ER α的表达，但不影响ER β的表达。Cd也增加了ERK1/2、Akt和PDGFR α的磷酸化，而ICI则阻断了它。由于磷酸化的刺激比预期的要慢，我们分析了c-fos和c-jun原癌基因以及PDGFA。Cd迅速增加c-jun、c-fos和PDGFA的表达。细胞也与Cd和特定激酶抑制剂共孵育，这阻断了Cd刺激的增殖。总之，我们的研究结果表明，Cd可能通过ER α依赖机制激活c-fos、c-jun和PDGFA，通过刺激Akt、ERK1/2和PDGFR α激酶活性来促进体外BC细胞增殖。2006爱思唯尔爱尔兰有限公司版权所有。
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.