Oxygen‐regulated expression of the Wilms’ tumor suppressor Wt1 involves hypoxia‐inducible factor‐1 (HIF‐1)
Oxygen‐regulated expression of the Wilms’ tumor suppressor Wt1 involves hypoxia‐inducible factor‐1 (HIF‐1)
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肾母细胞瘤抑制因子 Wt1 的氧调节表达涉及缺氧诱导因子-1 (HIF-1)
DOI：
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
H. Scholz
中科院分区：
文献类型：
--
作者：
K. Wagner;N. Wagner;S. Wellmann;G. Schley;A. Bondke;H. Theres;H. Scholz
Wilms肿瘤基因Wt 1是肿瘤抑制基因中唯一的，因为它需要某些器官的发育。最近，我们描述了从头表达的Wt 1在心肌血管缺血大鼠心脏。本研究的目的是分析Wt 1的缺氧/缺血诱导机制。我们在这里表明，Wt 1 mRNA和蛋白质在暴露于常压缺氧（8% O2）的大鼠心脏和肾脏中上调。在缺氧大鼠的肾小管中检测到异位Wt 1免疫反应性，其也表达抗凋亡蛋白Bcl-2，并且比常氧肾脏中含有显著更少的TUNEL阳性细胞。Wt 1表达在骨肉瘤细胞系U-2 OS和Reh淋巴母细胞中增强，这些细胞分别在1%O2或存在CoCl 2和去铁胺的情况下生长。Wt 1基因的启动子能够介导响应缺氧的荧光素酶报告基因的表达。我们在Wt 1序列中鉴定了一个与缺氧诱导因子1（HIF-1）结合的缺氧反应元件，并且是CoCl 2和HIF-1激活Wt 1启动子所必需的。这些发现表明，Wt 1表达可以通过缺氧刺激，这涉及HIF-1激活Wt 1启动子。
The Wilms’ tumor gene Wt1 is unique among tumor suppressors because of its requirement for the development of certain organs. We recently described de novo expression of Wt1 in myocardial blood vessels of ischemic rat hearts. The purpose of this study was to analyze the mechanism(s) of hypoxic/ischemic induction of Wt1. We show here that Wt1 mRNA and protein is up‐regulated in the heart and kidneys of rats exposed to normobaric hypoxia (8% O2). Ectopic Wt1 immunoreactivity was detected in renal tubules of hypoxic rats, which also expressed the antiapoptotic protein Bcl‐2 and contained significantly fewer TUNEL‐positive cells than in normoxic kidneys. Wt1 expression was enhanced in the osteosarcoma line U‐2OS and in Reh lymphoblast cells that were grown either at 1% O2 or in the presence of CoCl2 and desferrioxamine, respectively. The promoter of the Wt1 gene was capable of mediating expression of a luciferase reporter in response to hypoxia. We identified a hypoxia‐responsive element in the Wt1 sequence that bound to hypoxia‐inducible factor‐1 (HIF‐1) and was required for activation of the Wt1 promoter by CoCl2 and HIF‐1. These findings demonstrate that Wt1 expression can be stimulated by hypoxia, which involves activation of the Wt1 promoter by HIF‐1.
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DOI：
10.1073/pnas.92.26.11960
发表时间：
1995-12-19
影响因子：
11.1
作者：
Englert, C;Vidal, M;Haber, DA
通讯作者：
Haber, DA
影响因子：
11.2
作者：
Stephen M. Hewitt;Shinshichi Hamada;Timothy J. McDonnell;F. Rauscher;Grady F. Saunders
通讯作者：
Stephen M. Hewitt;Shinshichi Hamada;Timothy J. McDonnell;F. Rauscher;Grady F. Saunders
DOI：
--
发表时间：
1994-07
期刊：
The American journal of pathology
影响因子：
--
作者：
D. Novack;S. Korsmeyer
通讯作者：
D. Novack;S. Korsmeyer
影响因子：
3.8
作者：
Leuenroth, SJ;Grutkoski, PS;Simms, HH
通讯作者：
Simms, HH
11p13 维尔姆斯肿瘤基因 WT1 的表达与维尔姆斯肿瘤的组织学类别相关。
DOI：
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发表时间：
1992
期刊：
The American journal of pathology
影响因子：
--
作者：
Gerald,WL;Gramling,TS;Sens,DA;Garvin,AJ
通讯作者：
Garvin,AJ