perfluorooctane sulfonate (PFOS) 和相关化合物诱导核受体4A1 (NR4A1) - 取决于致癌的发生
Amanuel Hailemariam1, Srijana Upadhyay1, Vinod Srivastava2
1Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, Texas 77843 , United States.
Chemical research in toxicology
|March 11, 2025
概括
像PFOS一样,多醇基物质 (PFAS) 作为孤儿核受体4A1 (NR4A1) 的配体起作用. 这种相互作用促进癌细胞生长和瘤发育,突出显示NR4A1是PFAS诱导瘤发生的关键标.
科学领域:
- 环境健康 环境健康
- 分子生物学分子生物学
- 毒理学 毒理学 毒理学
背景情况:
- 聚甲基物质 (PFAS) 是普遍存在的环境污染物,与各种疾病有关.
- 孤儿核受体4A1 (NR4A1) 是PFAS毒性的潜在目标.
研究的目的:
- 调查聚甲硫酸盐 (PFOS) 和相关化合物是否针对NR4A1.1.
- 阐明NR4A1在PFAS诱导的癌细胞增殖和瘤生长中的作用.
主要方法:
- 在实验室测试使用癌细胞系 (Rh30) 和无人性裸体小鼠模型.
- 结合体结合域 (LBD) 分析,细胞增殖,迁移和入侵测试.
- 染色体免疫沉 (ChIP) 评估NR4A1与基因促进体的结合.
主要成果:
- PFOS和相关化合物与NR4A1 LBD结合.
- PFOS诱导NR4A1依赖的癌细胞增殖,迁移和入侵.
- 在不降低NR4A1促进体结合的情况下,PFOS可上调NR4A1受调的基因,包括PAX3-FOXO1瘤基因.
结论:
- PFOS作为NR4A1.1.的直接连接体起作用.
- 通过NR4A1激活,PFOS增强瘤发生,这表明NR4A1是PFAS诱导癌症进展的关键调解者.
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