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用o,p'-滴滴涕、p,p'-滴滴涕或硫丹处理的MCF-7和MDA-MB-231细胞中雌激素、孕激素和雄激素反应基因的表达。

Expression of estrogen-, progesterone-, and androgen-responsive genes in MCF-7 and MDA-MB-231 cells treated with o,p'-DDT, p,p'-DDT, or endosulfan.

作者信息

Kalinina Tatiana S, Kononchuk Vladislav V, Gulyaeva Lyudmila F

机构信息

Institute of Molecular Biology and Biophysics, Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia.

出版信息

J Biochem Mol Toxicol. 2021 Jun;35(6):1-8. doi: 10.1002/jbt.22773. Epub 2021 Mar 16.

Abstract

Endocrine disruptors are a major concern due to their possible association with hormone-dependent carcinogenesis. Some examples of compounds with such properties are organochlorine pesticides (OCPs). OCPs are persistent pollutants with high lipophilicity, long half-life, and bioaccumulation potential. In the past, some of the most commonly used OCPs were dichlorodiphenyltrichloroethane (DDT) and endosulfan. Here, we investigated the effects of o,p'-DDT, p,p'-DDT, and endosulfan and of hormones estradiol, testosterone, and progesterone on the expression of estrogen, progesterone, and androgen receptors (ER, PR, and AR) and of their target genes (KLF4, VEGFA, CCND1, PRLR, CDKN1A, and BCL6) in MCF-7 and MDA-MB-231 cells. The results confirmed that under the action of the insecticides, there are dose- and time-dependent changes in the expression of these receptors and target genes. As corroborated by an experiment with ER, PR, and AR negative MDA-MB-231 cells, the change in the expression of KLF4, VEGFA, CCND1, and PRLR in MCF-7 cells treated with o,p'-DDT and the change in CDKN1A and PRLR expression in MCF-7 cells treated with p,p'-DDT are likely mediated by ER, PR, and AR pathways. In conclusion, we have identified some targets of DDT and endosulfan and confirmed that the effects of insecticides on the expression of these target genes differ for breast cancer cell lines with different receptor statuses.

摘要

内分泌干扰物因其可能与激素依赖性致癌作用相关联而备受关注。具有此类特性的化合物的一些例子是有机氯农药(OCPs)。OCPs是具有高亲脂性、长半衰期和生物累积潜力的持久性污染物。过去,一些最常用的OCPs是二氯二苯三氯乙烷(DDT)和硫丹。在此,我们研究了o,p'-DDT、p,p'-DDT和硫丹以及激素雌二醇、睾酮和孕酮对MCF-7和MDA-MB-231细胞中雌激素、孕激素和雄激素受体(ER、PR和AR)及其靶基因(KLF4、VEGFA、CCND1、PRLR、CDKN1A和BCL6)表达的影响。结果证实,在杀虫剂作用下,这些受体和靶基因的表达存在剂量和时间依赖性变化。通过对ER、PR和AR阴性的MDA-MB-231细胞进行的实验证实,用o,p'-DDT处理的MCF-7细胞中KLF4、VEGFA、CCND1和PRLR表达的变化以及用p,p'-DDT处理的MCF-7细胞中CDKN1A和PRLR表达的变化可能由ER、PR和AR途径介导。总之,我们确定了DDT和硫丹的一些靶点,并证实杀虫剂对这些靶基因表达的影响因具有不同受体状态的乳腺癌细胞系而异。

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