Visfatin has been originally identified as a growth factor for early stage B cells and recently known as an adipokine. Here, we report that hypoxia induces the visfatin mRNA and protein levels in MCF7 breast cancer cells. We also demonstrate that induction of visfatin gene is regulated by hypoxia-inducible factor-1alpha (HIF-1alpha). Moreover, 5'-flanking promoter region of human visfatin gene contains two functional HIF responsive elements (HREs), activating the expression of visfatin. Mutation of these HREs in the visfatin promoter abrogates activation of a luciferase reporter gene driven by visfatin promoter under hypoxia. Taken together, our results demonstrate that visfatin is a new hypoxia-inducible gene of which expression is stimulated through the interaction of HIF-1 with HRE sites in its promoter region.

译文

Visfatin最初被确定为早期b细胞的生长因子,最近被称为脂肪因子。在这里,我们报告了缺氧诱导MCF7乳腺癌细胞中的visfatin mRNA和蛋白质水平。我们还证明了内脂素基因的诱导受缺氧诱导factor-1alpha (HIF-1alpha) 的调节。此外,人visfatin基因的5' 侧翼启动子区域包含两个功能性HIF响应元件 (HREs),激活visfatin的表达。这些hre在内脂素启动子中的突变会在缺氧条件下废除由内脂素启动子驱动的荧光素酶报告基因的激活。总之,我们的结果表明,visfatin是一种新的缺氧诱导基因,其表达通过HIF-1与其启动子区域中的HRE位点相互作用而被刺激。

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