PMID- 12738801
OWN - NLM
STAT- MEDLINE
DCOM- 20030717
LR  - 20120215
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 17
IP  - 10
DP  - 2003 Jul
TI  - Oxygen-regulated expression of the Wilms' tumor suppressor Wt1 involves 
      hypoxia-inducible factor-1 (HIF-1).
PG  - 1364-6
AB  - 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.
FAU - Wagner, Kay-Dietrich
AU  - Wagner KD
AD  - Johannes-Muller-Institut fur Physiologie, Berlin, Germany.
FAU - Wagner, Nicole
AU  - Wagner N
FAU - Wellmann, Sven
AU  - Wellmann S
FAU - Schley, Gunnar
AU  - Schley G
FAU - Bondke, Anja
AU  - Bondke A
FAU - Theres, Heinz
AU  - Theres H
FAU - Scholz, Holger
AU  - Scholz H
LA  - eng
PT  - Journal Article
DEP - 20030508
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hif1a protein, rat)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 0 (WT1 Proteins)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Binding Sites
MH  - Bone Neoplasms/metabolism
MH  - Cell Hypoxia
MH  - Cell Line
MH  - DNA-Binding Proteins/*metabolism
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - In Situ Nick-End Labeling
MH  - Kidney Tubules/cytology/metabolism
MH  - Lymphocytes/metabolism
MH  - Models, Genetic
MH  - Nuclear Proteins/*metabolism
MH  - Osteosarcoma/metabolism
MH  - Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - *Transcription Factors
MH  - *Transcriptional Activation
MH  - Tumor Cells, Cultured
MH  - Up-Regulation
MH  - WT1 Proteins/biosynthesis/*genetics
EDAT- 2003/05/10 05:00
MHDA- 2003/07/18 05:00
CRDT- 2003/05/10 05:00
PHST- 2003/05/10 05:00 [pubmed]
PHST- 2003/07/18 05:00 [medline]
PHST- 2003/05/10 05:00 [entrez]
AID - 02-1065fje [pii]
AID - 10.1096/fj.02-1065fje [doi]
PST - ppublish
SO  - FASEB J. 2003 Jul;17(10):1364-6. doi: 10.1096/fj.02-1065fje. Epub 2003 May 8.