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首页> 外文期刊>Zeitschrift fur Arznei- und Gewurzpflanzen >Inter-Individual Variation in Response to Estrogen in Human Breast Explants
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Inter-Individual Variation in Response to Estrogen in Human Breast Explants

机译：响应人类乳房外植体雌激素的间间变异

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Exposure to estrogen is strongly associated with increased breast cancer risk. While all women are exposed to estrogen, only 12% are expected to develop breast cancer during their lifetime. These women may be more sensitive to estrogen, as rodent models have demonstrated variability in estrogen sensitivity. Our objective was to determine individual variation in expression of estrogen receptor (ER) and estrogen-induced responses in the normal human breast. Human breast tissue from female donors undergoing reduction mammoplasty surgery were collected for microarray analysis of ER expression. To examine estrogen-induced responses, breast tissue from 23 female donors were cultured ex- vivo in basal or 10 nM 17 beta-estradiol (E2) media for 4 days. Expression of ER genes (ESR1 and ESR2) increased significantly with age. E2 induced consistent increases in global gene transcription, but expression of target genes AREG, PGR, and TGF beta 2 increased significantly only in explants from nulliparous women. E2-treatment did not induce consistent changes in proliferation or radiation induced apoptosis. Responses to estrogen are highly variable among women and not associated with levels of ER expression, suggesting differences in intracellular signaling among individuals. The differences in sensitivity to E2-stimulated responses may contribute to variation in risk of breast cancer.
机译：暴露于雌激素与增加的乳腺癌风险强烈有关。虽然所有妇女暴露于雌激素，但预计只有12％的人在寿命期间会产生乳腺癌。这些女性对雌激素可能更敏感，因为啮齿动物模型表明了雌激素敏感性的可变性。我们的目的是确定正常人乳腺中雌激素受体（ER）和雌激素诱导的反应表达的个体变化。收集来自乳腺成形术手术的女性供体的人乳腺组织进行ER表达的微阵列分析。为了检查雌激素诱导的反应，将来自23例雌性供体的乳腺组织在基底或10nm17β-雌二醇（E2）培养基中培养4天。 ER基因的表达（ESR1和ESR2）随着年龄的增长而显着增加。 E2诱导全局基因转录的一致增加，但靶基因的表达ISG，PGR和TGFβ2只有在染色女性的外侧显着增加。 E2-治疗没有诱导增殖或辐射诱导的细胞凋亡的一致变化。对雌激素的反应是女性的高度变化，而不与ER表达水平无关，表明个体间的细胞内信号传导的差异。对E2刺激反应的敏感性的差异可能有助于乳腺癌风险的变化。

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