Cho Jungyoon, Bahn Jae-Jun, Park Mikyung, Ahn Woongshick, Lee Young Joo
College of Engineering, Institute of Biotechnology, Department of Bioscience and Biotechnology, Sejong University, Seoul 143-747, Republic of Korea.
J Steroid Biochem Mol Biol. 2006 Jul;100(1-3):18-23. doi: 10.1016/j.jsbmb.2006.03.002. Epub 2006 Jun 23.
The estrogen receptor (ER) plays an important role in breast cancer development and progression. Hypoxia has been shown to modulate the level of ERalpha expression, which is intimately associated with the biology of breast carcinomas. However, the effect of hypoxia on ERalpha-mediated transactivation is largely unknown. In this report, we have examined ligand-independent transcriptional activation of ERalpha by hypoxia. The hypoxia-induced ERalpha-mediated transcriptional response was inhibited by the ER antagonist ICI 182,780 as determined by transient expression of ERalpha and ER-responsive reporter plasmids in the HEK 293 cells. Hypoxic activation of ERalpha was dependent on the increased expression of hypoxia-inducible factor-1alpha (HIF-1alpha), as examined in HEK 293 cells under conditions of normoxia. These results indicate that hypoxia activates ERalpha in a ligand-independent manner, possibly through the interaction between HIF-1alpha and ERalpha.
雌激素受体（ER）在乳腺癌的发生和发展中起着重要作用。缺氧已被证明可调节ERα的表达水平，这与乳腺癌的生物学特性密切相关。然而，缺氧对ERα介导的反式激活的影响在很大程度上尚不清楚。在本报告中，我们研究了缺氧对ERα的非配体依赖性转录激活作用。通过在HEK 293细胞中瞬时表达ERα和ER反应性报告质粒确定，ER拮抗剂ICI 182,780可抑制缺氧诱导的ERα介导的转录反应。在常氧条件下对HEK 293细胞进行检测，发现ERα的缺氧激活依赖于缺氧诱导因子-1α（HIF-1α）表达的增加。这些结果表明，缺氧可能通过HIF-1α与ERα之间的相互作用以非配体依赖性方式激活ERα。
