PMID- 17563752
OWN - NLM
STAT- MEDLINE
DCOM- 20080109
LR  - 20220317
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 26
IP  - 54
DP  - 2007 Nov 29
TI  - Significance of HIF-1-active cells in angiogenesis and radioresistance.
PG  - 7508-16
AB  - Human solid tumors contain hypoxic regions that have considerably lower oxygen 
      tension than the normal tissues. Hypoxia offers resistance to radiotherapy and 
      anticancer chemotherapy, as well as predispose to increased tumor metastases. 
      Furthermore, hypoxia induces hypoxia-inducible factor-1 (HIF-1), which in turn 
      increases tumor angiogenesis. Thus, eradication of HIF-1-active/hypoxic tumor 
      cells is very important for cancer therapy. We have previously reported that 
      procaspase-3 fused with a von Hippel-Lindau (VHL)-mediated protein destruction 
      motif of alpha subunit of HIF-1 (HIF-1alpha) containing Pro564, named 
      TAT-ODD-procaspase-3 (TOP3), specifically induced cell death to hypoxic cells in 
      vivo as well as in vitro. We now report that TOP3 also eradicates the 
      radiation-induced HIF-1-active tumor cells. HIF-1 activity in the xenografts of 
      human tumor cells, which express luciferase under the transcriptional control of 
      HIF-1, were monitored and quantified daily with an in vivo bioluminescence 
      photon-counting device. HIF-1 activity in tumors was more rapidly increased by 
      ionizing radiation (IR) compared to untreated tumors. TOP3 efficiently decreased 
      the HIF-1-activity in irradiated tumors as well as unirradiated ones, indicating 
      TOP3 eradicated tumor cells with HIF-1-activity induced by IR as well as hypoxia. 
      Eradication of HIF-1-active/hypoxic cells in the xenografts during irradiation 
      exhibited significant suppression in angiogenesis and strong enhancement in a 
      long-term growth suppression of tumor xenografts. These results further 
      strengthen the argument that HIF-1-active/hypoxic cells play crucial roles in 
      angiogenesis and radioresistance.
FAU - Harada, H
AU  - Harada H
AD  - Department of Radiation Oncology and Image-Applied Therapy, Kyoto University 
      Graduate School of Medicine, Kyoto, Japan.
FAU - Kizaka-Kondoh, S
AU  - Kizaka-Kondoh S
FAU - Li, G
AU  - Li G
FAU - Itasaka, S
AU  - Itasaka S
FAU - Shibuya, K
AU  - Shibuya K
FAU - Inoue, M
AU  - Inoue M
FAU - Hiraoka, M
AU  - Hiraoka M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070611
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (TOP3 fusion protein)
SB  - IM
MH  - Adenocarcinoma/pathology/physiopathology/prevention & control
MH  - Animals
MH  - Cell Death
MH  - *Cell Hypoxia
MH  - Cell Line, Tumor
MH  - Female
MH  - HeLa Cells
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha 
      Subunit/deficiency/genetics/*physiology/radiation effects
MH  - Mice
MH  - Mice, Transgenic
MH  - Neovascularization, Pathologic/prevention & control
MH  - Pancreatic Neoplasms/pathology/*physiopathology/prevention & control
MH  - Promoter Regions, Genetic
MH  - Radiation, Ionizing
MH  - Recombinant Fusion Proteins/physiology
MH  - Transplantation, Heterologous
MH  - Uterine Cervical Neoplasms/pathology/physiopathology/prevention & control
EDAT- 2007/06/15 09:00
MHDA- 2008/01/10 09:00
CRDT- 2007/06/15 09:00
PHST- 2007/06/15 09:00 [pubmed]
PHST- 2008/01/10 09:00 [medline]
PHST- 2007/06/15 09:00 [entrez]
AID - 1210556 [pii]
AID - 10.1038/sj.onc.1210556 [doi]
PST - ppublish
SO  - Oncogene. 2007 Nov 29;26(54):7508-16. doi: 10.1038/sj.onc.1210556. Epub 2007 Jun 
      11.