ELL is an HIF-1alpha partner that regulates and responds to hypoxia response in PC3 cells.
ELL is an HIF-1alpha partner that regulates and responds to hypoxia response in PC3 cells.
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DOI：
10.1002/pros.21113
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发表时间：
2010-05-15
期刊：
影响因子：
2.8
通讯作者：
Wang, Zhou
中科院分区：
文献类型：
--
作者：
Liu, Lingqi;Ai, Junkui;Xiao, Wuhan;Liu, June;Wang, Yujuan;Xin, Dianqi;He, Zhisong;Guo, Yinglu;Wang, Zhou
ELL在肿瘤发生和动物发育中发挥着重要作用。 HIF-1 是一种转录因子，充当 O2 稳态的主要调节因子。我们之前的研究表明，ELL 的结合伴侣 U19/Eaf2 可以调节 HIF-1α 活性和缺氧反应，表明 ELL 也可能影响 HIF-1α 通路和缺氧反应。进行共定位和免疫共沉淀来测试 ELL 和 HIF-1α 之间的相互作用。使用慢病毒表达系统建立了具有稳定 ELL 敲低的 PC3 细胞和具有稳定 ELL 过表达的 PC3 细胞及其对照。通过Western blot和Real-time PCR检测ELL对HIF-1α蛋白及其下游基因转录的影响。为了阐明缺氧对 ELL 的潜在影响，使用具有稳定 ELL 过表达的 PC3 亚系进行细胞生长和集落形成测定。 ELL 与转染细胞中的 HIF-1α 相关。在 PC3 前列腺癌细胞中，ELL 抑制 HIF-1α 蛋白水平和下游基因表达。正如预期的那样，ELL 在常氧条件下抑制细胞生长和集落形成。有趣的是，在缺氧条件下抑制作用减轻。我们的研究结果表明，ELL 和 HIF-1α 是结合伙伴，可以在缺氧情况下调节彼此的功能。
ELL plays an important role in tumorigenesis and animal development. HIF-1 is a transcriptional factor that functions as a master regulator of O2 homeostasis. Our previous studies showed that a binding partner of ELL, U19/Eaf2, can modulate HIF-1α activity and hypoxia response, suggesting that ELL may also influence HIF-1α pathway and hypoxia response. Co-localization and co-immunoprecipitation were performed to test the interaction between ELL and HIF-1α. PC3 cells with stable ELL knockdown and PC3 cells with stable ELL overexpression, along with their controls, were established using lentiviral expression system. Western blot and Real-time PCR were performed to test the effect of ELL on HIF-1α protein and its down-stream gene transcription. To elucidate potential effect of hypoxia on ELL, cell growth and colony formation assay were performed using PC3 subline with stable ELL overexpression. ELL is associated with HIF-1α in transfected cells. In PC3 prostate cancer cells, ELL inhibited HIF-1α protein level and down-stream gene expression. As expected, ELL inhibited cell growth and colony formation under normoxia. Interestingly, the inhibition was alleviated under hypoxia. Our findings suggest that ELL and HIF-1α are binding partners and can modulate the functions of each other in hypoxia.
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