交易激励
雌激素受体
雌激素受体α
探地雷达
基因沉默
雌激素受体
雌激素
信号转导
生物
细胞生物学
内分泌干扰物
癌症研究
化学
药理学
内分泌学
基因表达
内分泌系统
生物化学
激素
基因
遗传学
癌症
乳腺癌
作者
M. Drouault,Claude Delalande,Hélène Bouraïma-Lelong,Virginie Séguin,David Garon,Vincent Hanoux
标识
DOI:10.1016/j.fct.2022.113127
摘要
Deoxynivalenol (DON), which is one of the prevalent mycotoxins in food and feeds, exerts adverse effects on animal and human health. These effects are mainly associated with its ribotoxic properties, although few studies suggest the involvement of other mechanisms of action. To assess the ability of DON to disrupt estrogen signaling, we conducted an in vitro study using MCF-7 and MDA-MB-231 cells. After 72h, DON reduced cell viability in both cell lines, thus highlighting its well-known cytotoxic effect. However, after 6h, DON increased the expression of estrogen-responsive genes, hence demonstrating the stimulation of estrogen signaling by this mycotoxin after a short-term exposure. This effect was partially reversed by siRNA-mediated silencing of ERα expression and by 4-hydroxytamoxifen (ERα antagonist), but neither by G36 (GPER antagonist) nor by the siRNA-mediated silencing of PPARγ2 expression. Moreover, DON exposure induced an increase in the level of ERα phosphorylation at serine 167. Furthermore, when combined with zearalenone (a naturally co-occurring mycotoxin recognized as an endocrine disruptor), DON increased the expression of estrogen-responsive genes to a greater extent than each individual compound taken separately. Taken together, our results suggest, for the first time, that DON can disrupt estrogen signaling through the ligand-independent activation of ERα.
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