Canonical Wnt signaling is critical to estrogen-mediated uterine growth
Canonical Wnt signaling is critical to estrogen-mediated uterine growth
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DOI：
10.1210/me.2004-0259
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发表时间：
2004-12-01
影响因子：
--
通讯作者：
Das, SK
中科院分区：
文献类型：
--
作者：
Hou, XN;Tan, Y;Das, SK
雌激素在子宫中的主要生物效应被认为主要由核雌激素受体 ERα 和 ERβ 介导。我们在此表明，雌激素以不依赖于 ER 的方式快速上调小鼠子宫中 Wnt 家族的 Wnt4 和 Wnt5a 以及 Wnt 受体家族的 frizzled-2 的表达。 Wnt 介导经典信号传导的机制之一涉及细胞内 β-连环蛋白的稳定。我们观察到雌激素治疗促进活性β-连环蛋白在子宫上皮细胞核定位。我们还发现，腺病毒介导的 Wnt 拮抗剂 SFRP-2 的体内递送，下调雌激素依赖性β-连环蛋白活性，而不影响一些早期效应（吸水和血管生成标记物），并抑制子宫上皮细胞生长，这表明经典的 Wnt 信号传导对于雌激素诱导的子宫生长至关重要。我们目前的结果为雌激素的新作用提供了证据，雌激素以不依赖于 ER 的方式靶向早期 Wnt/β-连环蛋白信号传导，以调节依赖于 ER 的晚期子宫生长反应。
Major biological effects of estrogen in the uterus are thought to be primarily mediated by nuclear estrogen receptors, ERalpha and ERbeta. We show here that estrogen in an ER-independent manner rapidly up-regulates the expression of Wnt4 and Wnt5a of the Wnt family and frizzled-2 of the Wnt receptor family in the mouse uterus. One of the mechanisms by which Wnts mediate canonical signaling involves stabilization of intracellular beta-catenin. We observed that estrogen treatment prompts nuclear localization of active beta-catenin in the uterine epithelium. We also found that adenovirus mediated in vivo delivery of SFRP-2, a Wnt antagonist, downregulates estrogen-dependent beta-catenin activity without affecting some of the early effects ( water imbibition and angiogenic markers) and inhibits uterine epithelial cell growth, suggesting that canonical Wnt signaling is critical to estrogen-induced uterine growth. Our present results provide evidence for a novel role of estrogen that targets early Wnt/beta-catenin signaling in an ER-independent manner to regulate the late uterine growth response that is ER dependent.