Estrogenicity of bisphenol A in a human endometrial carcinoma cell line

Estrogenicity of bisphenol A in a human endometrial carcinoma cell line
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DOI:
10.1016/s0303-7207(98)00202-0
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发表时间:
1999-04-25
影响因子:
4.1
通讯作者:
Gaido, KW
Gaido, KW
中科院分区:
医学2区
文献类型:
--
作者:
Bergeron, RM;Thompson, TB;Gaido, KW

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在人子宫内膜细胞系ECC-1中检测了双酚A(BPA)对人雌激素受体(ER)结合、孕激素受体(PR)mRNA和蛋白表达以及细胞增殖的影响。尽管BPA的效力低于17β-雌二醇,但它能够与人子宫ER结合。双酚A还能诱导mRNA和蛋白质达到与雌二醇相似的水平。ICI可拮抗BPA介导的PR基因表达,提示这可能是ER介导的信号转导途径。最后,与赋形剂对照组相比,雌二醇组的细胞数增加了2倍,而双酚A组的细胞数没有变化。用ICI 182,780(ICI)或BPA处理可抑制E_2的增加,提示有相似的结合部位。虽然ER结合相似,但E2同时影响增殖和PR的表达,而BPA只影响PR基因的表达。这项研究的结果提供了证据,表明两种ER激动剂在体外可以不同地作用于调节细胞生长和发育的基因的表达,尽管人类的风险潜力仍有待确定。(C)1999爱思唯尔爱尔兰科学有限公司保留所有权利。
The ability of bisphenol A (BPA) to affect human estrogen receptor (ER) binding, expression of progesterone receptor (PR) mRNA and protein, and cell proliferation has been measured in the human endometrial cell line,ECC-1. Although less potent than 17 beta-estradiol, BPA was able to bind to the human uterine ER. BPA also induced both mRNA and protein to levels similar to E2. BPA-mediated PR mRNA induction was antagonized by ICI, suggesting an ER-mediated pathway. Finally, E2 produced a 2-fold increase in cell number, while BPA showed no difference compared with vehicle control. The increase by E2 was inhibited by treatment with the either ICI 182,780 (ICI) or BPA, suggesting similar binding sites. Although ER binding is similar, E2 affected both proliferation and PR expression, while BPA only affected PR gene expression. The results of this study provide evidence that two ER agonists can act differentially in vitro to affect the expression of genes involved in regulating cellular growth and development, though the human risk potential remains to be determined. (C) 1999 Elsevier Science Ireland Ltd. Ail rights reserved.