Hypoxic activation of unoccupied estrogen-receptor-alpha is mediated by hypoxia-inducible factor-1 alpha
Hypoxic activation of unoccupied estrogen-receptor-alpha is mediated by hypoxia-inducible factor-1 alpha
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DOI：
10.1016/j.jsbmb.2006.03.002
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发表时间：
2006-07-01
影响因子：
4.1
通讯作者：
Lee, Young Joo
中科院分区：
文献类型：
--
作者：
Cho, Jungyoon;Bahn, Jae-Jun;Lee, Young Joo
雌激素受体(ER)在乳腺癌的发生发展中起着重要作用。低氧已被证明可以调节ERα的表达水平，这与乳腺癌的生物学特性密切相关。然而，低氧对ERα介导的反式激活的影响在很大程度上是未知的。在这份报告中，我们研究了低氧对ERα的非配体依赖的转录激活。ER拮抗剂10182,780可以抑制缺氧诱导的ERα介导的转录反应，这是通过Era和ER反应报告质粒在HEK 293细胞中的瞬时表达确定的。ERα的低氧激活依赖于低氧诱导因子-1α(HIF-1α)的表达增加，正如在常氧条件下在HEK 293细胞中所检测的那样。这些结果表明，缺氧可能通过HIF-1α和ERα之间的相互作用，以一种不依赖于配体的方式激活ERα。(C)2006爱思唯尔有限公司。保留所有权利。
The estrogen receptor (ER) plays an important role in breast cancer development and progression. Hypoxia has been shown to modulate the level of ER alpha expression, which is intimately associated with the biology of breast carcinomas. However, the effect of hypoxia on ER alpha-mediated transactivation is largely unknown. In this report, we have examined ligand-independent transcriptional activation of ER alpha by hypoxia. The hypoxia-induced ER alpha-mediated transcriptional response was inhibited by the ER antagonist 10 182,780 as determined by transient expression of ERa and ER-responsive reporter plasmids in the HEK 293 cells. Hypoxic activation of ER alpha was dependent on the increased expression of hypoxia-inducible factor-la (HIF-1 alpha), as examined in HEK 293 cells under conditions of normoxia. These results indicate that hypoxia activates ER alpha in a ligand-independent manner, possibly through the interaction between HIF-1 alpha and ER alpha. (c) 2006 Elsevier Ltd. All rights reserved.