PMID- 17624305
OWN - NLM
STAT- MEDLINE
DCOM- 20071001
LR  - 20131121
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 360
IP  - 4
DP  - 2007 Sep 7
TI  - The combination of hypoxia-response enhancers and an oxygen-dependent proteolytic 
      motif enables real-time imaging of absolute HIF-1 activity in tumor xenografts.
PG  - 791-6
AB  - The transcriptional activity of hypoxia-inducible factor-1 (HIF-1) is associated 
      with tumor malignancies; therefore, it is important to comprehend its dynamism in 
      solid tumors. However, a molecular imaging strategy to accurately access it 
      remains to be developed. We constructed here a novel HIF-1-dependent reporter 
      gene, 5HREp-ODD-luc, in which 5 copies of the hypoxia-response element (5HRE) 
      enhance expression of the oxygen-dependent degradation (ODD) domain and 
      luciferase (luc) fusion under hypoxia. Because the ODD domain caused the 
      oxygen-dependent degradation of the ODD-Luc protein, the novel reporter gene 
      showed little leak of luminescence under normoxia. Such a property caused an 
      increase of the hypoxia-responsiveness up to about 4.7 x 10(4) -fold. Moreover, 
      the ODD domain caused rapid degradation of the ODD-Luc protein under normoxia, 
      the luminescence reflected the dynamism of HIF-1 activity in real-time. The 
      superiority of the novel reporter gene will surely accelerate analysis of the 
      intratumoral HIF-1 activity during tumor progression and cancer treatments.
FAU - Harada, Hiroshi
AU  - Harada H
AD  - Department of Radiation Oncology and Image-Applied Therapy, Kyoto University 
      Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, 
      Japan. hharada@kuhp.kyoto-u.ac.jp
FAU - Kizaka-Kondoh, Shinae
AU  - Kizaka-Kondoh S
FAU - Itasaka, Satoshi
AU  - Itasaka S
FAU - Shibuya, Keiko
AU  - Shibuya K
FAU - Morinibu, Akiyo
AU  - Morinibu A
FAU - Shinomiya, Kazumi
AU  - Shinomiya K
FAU - Hiraoka, Masahiro
AU  - Hiraoka M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070705
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (DNA Primers)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Base Sequence
MH  - Cell Hypoxia/*drug effects
MH  - DNA Primers
MH  - Genes, Reporter
MH  - HeLa Cells
MH  - Humans
MH  - Hydrolysis
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Neoplasms/*metabolism
MH  - Oxygen/*metabolism
MH  - Transplantation, Heterologous
EDAT- 2007/07/13 09:00
MHDA- 2007/10/02 09:00
CRDT- 2007/07/13 09:00
PHST- 2007/06/20 00:00 [received]
PHST- 2007/06/21 00:00 [accepted]
PHST- 2007/07/13 09:00 [pubmed]
PHST- 2007/10/02 09:00 [medline]
PHST- 2007/07/13 09:00 [entrez]
AID - S0006-291X(07)01390-3 [pii]
AID - 10.1016/j.bbrc.2007.06.149 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2007 Sep 7;360(4):791-6. doi: 
      10.1016/j.bbrc.2007.06.149. Epub 2007 Jul 5.