Bae Soo-Kyung, Kim Su-Ryun, Kim Jong Gab, Kim Jee Yeon, Koo Tae Hyeon, Jang Hye-Ock, Yun Il, Yoo Mi-Ae, Bae Moon-Kyoung
College of Dentistry and Research Institute for Oral Biotechnology, Pusan National University, Pusan 602-739, South Korea.
FEBS Lett. 2006 Jul 24;580(17):4105-13. doi: 10.1016/j.febslet.2006.06.052. Epub 2006 Jun 30.
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.
内脂素最初被鉴定为早期B细胞的生长因子，最近被认为是一种脂肪因子。在此，我们报告缺氧可诱导MCF7乳腺癌细胞中内脂素的mRNA和蛋白水平。我们还证明内脂素基因的诱导受缺氧诱导因子-1α（HIF-1α）调控。此外，人内脂素基因的5'-侧翼启动子区域包含两个功能性缺氧反应元件（HREs），可激活内脂素的表达。内脂素启动子中这些HREs的突变消除了缺氧条件下由内脂素启动子驱动的荧光素酶报告基因的激活。综上所述，我们的结果表明内脂素是一种新的缺氧诱导基因，其表达通过HIF-1与其启动子区域的HRE位点相互作用而受到刺激。
