Modulation of gene expression and endocrine response pathways by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds.
Modulation of gene expression and endocrine response pathways by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds.
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DOI：
10.1016/0163-7258(95)00017-b
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发表时间：
1995
影响因子：
13.5
通讯作者：
S. Safe
中科院分区：
文献类型：
--
作者：
S. Safe
芳烃（Ah）受体结合几种不同结构类别的化学物质，包括卤代芳烃，以2,3,7,8-四氯二苯并-对二恶英（TCDD）为代表，多核芳烃和杂多核芳烃。TCDD诱导包括CYP1A1在内的几个基因的表达，分子生物学研究表明，Ah受体作为核配体诱导的转录因子，与位于应答基因5 '侧区的外源或二恶英应答元件相互作用。在啮齿动物和人类乳腺癌细胞系中，TCDD还引起多种毒性作用，调节内分泌通路并抑制雌激素（17β-雌二醇）诱导的广谱反应。分子生物学研究表明，TCDD通过核Ah受体与该基因的雌激素受体- Spl增强子序列中不完善的二恶英响应元件的靶向相互作用，抑制17β-雌二醇诱导的组织蛋白酶D基因的表达。
The aryl hydrocarbon (Ah) receptor binds several different structural classes of chemicals, including halogenated aromatics, typified by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polynuclear aromatic and heteropolynuclear aromatic hydrocarbons. TCDD induces expression of several genes including CYP1A1, and molecular biology studies show that the Ah receptor acts as a nuclear ligand-induced transcription factor that interacts with xenobiotic or dioxin responsive elements located in 5′-flanking regions of responsive genes. TCDD also elicits diverse toxic effects, modulates endocrine pathways and inhibits a broad spectrum of estrogen (17β-estradiol)-induced responses in rodents and human breast cancer cell lines. Molecular biology studies show that TCDD inhibited 17β-estradiol-induced cathepsin D gene expression by targeted interaction of the nuclear Ah receptor with imperfect dioxin responsive elements strategically located within the estrogen receptor — Spl enhancer sequence of this gene.