Profile of Estrogen-Responsive Genes in an Estrogen-Specific Mammary Gland Outgrowth Model
Profile of Estrogen-Responsive Genes in an Estrogen-Specific Mammary Gland Outgrowth Model
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DOI：
10.1002/mrd.21041
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发表时间：
2009-08-01
影响因子：
2.5
通讯作者：
Korach, Kenneth S.
中科院分区：
文献类型：
--
作者：
Deroo, Bonnie J.;Hewitt, Sylvia C.;Korach, Kenneth S.
小鼠乳腺的青春期发育需要卵巢和脑下垂体激素。雌二醇引导导管伸长和分支，孕酮引导第三级分支和肺泡发育。这项研究的目的是在没有其他卵巢激素的情况下和不同发育阶段的小鼠乳腺中确定与青春期导管生长相关的雌激素反应基因。我们假设雌激素诱导的基因及其相关功能在导管延长的早期阶段与显着的导管延长发生后诱导的基因及其相关功能是不同的。因此，将去卵巢的青春期前小鼠暴露于17β-雌二醇2~28天，并在此期间的不同时间用基因芯片分析乳腺整体基因的表达。我们发现：(A)在我们的纯雌激素模型中，基因表达的变化模拟了正常小鼠青春期发育中发生的那些变化，(B)在不同程度的导管延长中观察到了不同和重叠的基因图谱，以及(C)细胞增殖、免疫反应和代谢/分解代谢是与乳腺导管生长相关的最常见的功能类别。尤其引人注目的是一项新的观察结果，即在碳水化合物代谢过程中活跃的基因对雌二醇的反应迅速而有力地减少。最后，我们确定了在人类乳腺癌中也与雌激素受体a共表达的乳腺雌激素反应基因。总之，我们的基因组数据支持雌激素是青春期乳腺发育过程中驱动导管延长的主要激素信号之一的生理学观察。
Both ovarian and pituitary hormones are required for the pubertal development of the mouse mammary gland. Estradiol directs ductal elongation and branching, while progesterone leads to tertiary branching and alveolar development. The purpose of this investigation was to identify estrogen-responsive genes associated with pubertal ductal growth in the mouse mammary gland in the absence of other ovarian hormones and at different stages of development. We hypothesized that the estrogen-induced genes and their associated functions at early stages of ductal elongation would be distinct from those induced after significant ductal elongation had occurred. Therefore, ovariectomized prepubertal mice were exposed to 17 beta-estradiol from two to 28 days, and mammary gland global gene expression analyzed by microarray analysis at various times during this period. We found that: (a) gene expression changes in our estrogen-only model mimic those changes that occur in normal pubertal development in intact mice, (b) both distinct and overlapping gene profiles were observed at varying extents of ductal elongation, and (c) cell proliferation, the immune response, and metabolism/catabolism were the most common functional categories associated with mammary ductal growth. Particularly striking was the novel observation that genes active during carbohydrate metabolism were rapidly and robustly decreased in response to estradiol. Lastly, we identified mammary estradiol-responsive genes that are also co-expressed with estrogen receptor a in human breast cancer. In conclusion, our genomic data support the physiological observation that estradiol is one of the primary hormonal signals driving ductal elongation during pubertal mammary development.