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首页> 外文期刊>Cancer letters >Hypoxia-inducible factor 1 alpha mediates epidermal growth factor-induced down-regulation of E-cadherin expression and cell invasion in human ovarian cancer cells
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Hypoxia-inducible factor 1 alpha mediates epidermal growth factor-induced down-regulation of E-cadherin expression and cell invasion in human ovarian cancer cells

机译：缺氧诱导因子1α介导表皮生长因子诱导人卵巢癌细胞中E-钙粘蛋白表达下调和细胞侵袭

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Hypoxia-inducible factor 1?? (HIF-1??) regulates the transcription of a number of genes under hypoxia and other extracellular stimulations. It has been shown that E-cadherin is down-regulated by epidermal growth factor receptor (EGF) stimulation, and that cells with low E-cadherin expression are more invasive. Our recent study demonstrated a novel mechanism by which EGF down-regulates E-cadherin expression through production of hydrogen peroxide (H2O2) and the activation of p38 MAPK in human ovarian cancer cells. In this study, we were interested in examining the potential role of HIF-1?? in cell invasion under normoxic conditions, specifically when cells are treated with EGF, which is known to down-regulate E-cadherin and increase invasiveness. We show that EGF treatment induces HIF-1?? expression in two human ovarian cancer cell lines (SKOV3 and OVCAR5), and that this effect is diminished by treatment with a membrane-permeable H2O2 scavenger, PEG-catalase. However, the induction of HIF-1?? by EGF did not require the activation of p38 MAPK. Treatment with siRNA targeting HIF-1?? reduces both basal and EGF-induced HIF-1?? levels. Importantly, treatment with HIF-1?? siRNA diminishes the up-regulation of Snail and Slug as well as the down-regulation of E-cadherin by EGF. The involvement of HIF-1?? in the down-regulation of E-cadherin was confirmed with cobalt chloride (CoCl2), a hypoxia-mimetic reagent. Finally, we also show that EGF-induced cell invasion is attenuated by treatment with HIF-1?? siRNA. This study demonstrates an important role for HIF-1?? in mediating the effects of EGF on Snail, Slug and E-cadherin expression as well as invasiveness in human ovarian cancer cells. ? 2012 Elsevier Ireland Ltd.
机译：缺氧诱导因子1？ （HIF-1α）在缺氧和其他细胞外刺激下调节许多基因的转录。已经表明，表皮生长因子受体（EGF）刺激下调了E-cadherin，而具有低E-cadherin表达的细胞更具侵袭性。我们最近的研究表明，EGF通过产生过氧化氢（H2O2）和激活人卵巢癌细胞中的p38 MAPK来下调E-cadherin表达。在这项研究中，我们有兴趣检查HIF-1的潜在作用？在常氧条件下，尤其是在用EGF处理细胞时，已知EGF会下调E-钙黏着蛋白并增加侵袭性。我们证明EGF治疗可诱导HIF-1 ？？？在两个人类卵巢癌细胞系（SKOV3和OVCAR5）中表达，并且通过用膜可渗透的H2O2清除剂PEG-过氧化氢酶处理减弱了这种作用。然而，HIF-1的诱导？通过EGF不需要激活p38 MAPK。用靶向HIF-1的siRNA进行治疗？降低基础和EGF诱导的HIF-1？水平。重要的是，用HIF-1进行治疗？ siRNA减少了EGF对Snail和Slug的上调以及对E-cadherin的下调。 HIF-1的参与？ E-cadherin的下调通过氯化钴（CoCl2）（一种缺氧模拟剂）得到了证实。最后，我们还表明，用HIF-1α2处理可减轻EGF诱导的细胞侵袭。 siRNA。这项研究证明了HIF-1的重要作用？介导EGF对人卵巢癌细胞Snail，Slug和E-cadherin表达以及侵袭性的影响。 ？ 2012爱思唯尔爱尔兰有限公司

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