Yi Jinhyung Michael, Kwon Hyeok Yi, Cho Jung Yoon, Lee Young Joo
Department of Bioscience and Biotechnology College of Engineering, Institute of Biotechnology, Sejong University, Kwang-Jin-Gu, Seoul, Republic of Korea.
Biochem Biophys Res Commun. 2009 Jan 23;378(4):842-6. doi: 10.1016/j.bbrc.2008.11.142. Epub 2008 Dec 11.
Hypoxia activates and degrades estrogen receptor alpha (ERalpha) in human breast cancer cells, which may play an important role in the development and progression of breast cancer. In this study, the synergistic effects of estrogen (E(2)) and hypoxia on ERalpha-mediated transactivation and ERalpha degradation were investigated. ERalpha-mediated transcriptional activity was synergistically increased by E(2) and hypoxia, as determined by the transient expression of ERalpha and ER-responsive reporter plasmids in HEK 293 cells. Twenty hours of E(2) and hypoxia treatment synergistically induced degradation of ERalpha by 95% via a proteasome-dependent pathway in MCF-7 cells. These results provide evidence that hypoxia may stimulate yet unknown factor(s), which can further stimulate ERalpha signal transduction pathways.
缺氧可激活并降解人乳腺癌细胞中的雌激素受体α（ERα），这可能在乳腺癌的发生和发展中起重要作用。在本研究中，研究了雌激素（E₂）和缺氧对ERα介导的反式激活及ERα降解的协同作用。通过在HEK 293细胞中瞬时表达ERα和ER反应性报告质粒确定，E₂和缺氧协同增加了ERα介导的转录活性。在MCF-7细胞中，20小时的E₂和缺氧处理通过蛋白酶体依赖性途径协同诱导ERα降解95%。这些结果证明，缺氧可能刺激未知因子，进而进一步刺激ERα信号转导途径。
