PMID- 20442286
OWN - NLM
STAT- MEDLINE
DCOM- 20100621
LR  - 20211028
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 70
IP  - 10
DP  - 2010 May 15
TI  - Hypoxia modulates EWS-FLI1 transcriptional signature and enhances the malignant 
      properties of Ewing's sarcoma cells in vitro.
PG  - 4015-23
LID - 10.1158/0008-5472.CAN-09-4333 [doi]
AB  - Hypoxia is an important condition in the tumor cell microenvironment and 
      approximately 1% to 1.5% of the genome is transcriptionally responsive to hypoxia 
      with hypoxia-inducible factor-1 (HIF-1) as a major mediator of transcriptional 
      activation. Tumor hypoxia is associated with a more aggressive phenotype of many 
      cancers in adults, but data on pediatric tumors are scarce. Because, by 
      immunohistochemistry, HIF-1alpha expression was readily detectable in 18 of 28 
      primary Ewing's sarcoma family tumors (ESFT), a group of highly malignant 
      bone-associated tumors in children and young adults, we studied the effect of 
      hypoxia on ESFT cell lines in vitro. Intriguingly, we found that EWS-FLI1 protein 
      expression, which characterizes ESFT, is upregulated by hypoxia in a 
      HIF-1alpha-dependent manner. Hypoxia modulated the EWS-FLI1 transcriptional 
      signature relative to normoxic conditions. Both synergistic as well as 
      antagonistic transcriptional effects of EWS-FLI1 and of hypoxia were observed. 
      Consistent with alterations in the expression of metastasis-related genes, 
      hypoxia stimulated the invasiveness and soft agar colony formation of ESFT cells 
      in vitro. Our data represent the first transcriptome analysis of hypoxic ESFT 
      cells and identify hypoxia as an important microenvironmental factor modulating 
      EWS-FLI1 expression and target gene activity with far-reaching consequences for 
      the malignant properties of ESFT.
CI  - (c)2010 AACR.
FAU - Aryee, Dave N T
AU  - Aryee DN
AD  - Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, 
      Austria. dave.aryee@ccri.at
FAU - Niedan, Stephan
AU  - Niedan S
FAU - Kauer, Maximilian
AU  - Kauer M
FAU - Schwentner, Raphaela
AU  - Schwentner R
FAU - Bennani-Baiti, Idriss M
AU  - Bennani-Baiti IM
FAU - Ban, Jozef
AU  - Ban J
FAU - Muehlbacher, Karin
AU  - Muehlbacher K
FAU - Kreppel, Michael
AU  - Kreppel M
FAU - Walker, Robert L
AU  - Walker RL
FAU - Meltzer, Paul
AU  - Meltzer P
FAU - Poremba, Christopher
AU  - Poremba C
FAU - Kofler, Reinhard
AU  - Kofler R
FAU - Kovar, Heinrich
AU  - Kovar H
LA  - eng
GR  - Z01 BC010759-03/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100504
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (EWS-FLI fusion protein)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Proto-Oncogene Protein c-fli-1)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Protein EWS)
SB  - IM
MH  - Biomarkers, Tumor/*genetics/metabolism
MH  - Blotting, Western
MH  - Bone Neoplasms/*genetics/pathology
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic/*physiology
MH  - Gene Regulatory Networks
MH  - Humans
MH  - Hypoxia/*metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism
MH  - Immunoenzyme Techniques
MH  - Oligonucleotide Array Sequence Analysis
MH  - Oncogene Proteins, Fusion/*genetics
MH  - Proto-Oncogene Protein c-fli-1/*genetics
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA-Binding Protein EWS
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sarcoma, Ewing/*genetics/pathology
MH  - Transcriptional Activation
PMC - PMC2884367
MID - NIHMS191004
EDAT- 2010/05/06 06:00
MHDA- 2010/06/22 06:00
PMCR- 2011/05/15
CRDT- 2010/05/06 06:00
PHST- 2010/05/06 06:00 [entrez]
PHST- 2010/05/06 06:00 [pubmed]
PHST- 2010/06/22 06:00 [medline]
PHST- 2011/05/15 00:00 [pmc-release]
AID - 0008-5472.CAN-09-4333 [pii]
AID - 10.1158/0008-5472.CAN-09-4333 [doi]
PST - ppublish
SO  - Cancer Res. 2010 May 15;70(10):4015-23. doi: 10.1158/0008-5472.CAN-09-4333. Epub 
      2010 May 4.