暴露会通过E2F2/FZD10轴诱导人类正常乳腺上皮细胞的干细胞
Yang Yang1, Dexiu Hu1, Maoyuan Gong1
1The key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, 550025, China.
概括
长期暴露于可以通过产生癌症干细胞来促进乳腺癌的发展. 这项研究确定了E2F2 / FZD10通路作为关键机制,将与这种危险的细胞转化联系起来.
科学领域:
- 环境健康 环境健康
- 癌症生物学 癌症生物学
- 分子毒理学 分子毒理学
背景情况:
- 慢性暴露与全身毒性和癌症风险有关.
- 关联与乳腺癌的具体机制尚不清楚.
研究的目的:
- 为了研究低剂量暴露如何影响人类乳腺上皮细胞.
- 确定涉及诱导乳腺癌干细胞类表型的分子途径.
主要方法:
- 人类乳腺上皮细胞 (MCF-10A) 暴露于低剂量的甲 (NaAsO2).
- 评估了细胞迁移,入侵,球体形成和癌症干细胞标志物表达.
- 转录基因分析和功能研究确定了关键的分子介导体.
主要成果:
- 暴露增强了细胞迁移,入侵和球体形成.
- 关键的乳腺癌干细胞 (BCSC) 标志物 (EpCAM,ALDH1,CD44+/CD24-/低) 的上调.
- E2F2被确定为调节FZD10并激活Wnt/β-catenin通路的调解者.
结论:
- 暴露于酸盐会将乳腺细胞重新编程为类似BCSC的表型.
- E2F2/FZD10轴是诱导的乳腺癌中一种新的分子途径.
- 这一途径代表了预防相关乳腺癌风险的潜在目标.
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