PMID- 15150104
OWN - NLM
STAT- MEDLINE
DCOM- 20040802
LR  - 20211203
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 64
IP  - 10
DP  - 2004 May 15
TI  - Akt and hypoxia-inducible factor-1 independently enhance tumor growth and 
      angiogenesis.
PG  - 3500-7
AB  - Recent reports have suggested that phosphatidylinositol 3-kinase/Akt signaling 
      can induce angiogenesis and tumor growth by activating the hypoxia-inducible 
      factor-1 (HIF-1). However, the absence of specific biochemical inhibitors of 
      HIF-1 signaling has prevented a direct test of the requirement for HIF-1 activity 
      in Akt-dependent tumorigenesis. To genetically test the relationship between 
      HIF-1 and Akt, activated Akt was expressed in a hepatoma cell line lacking HIF-1. 
      Akt expression was associated with a dramatic increase in tumor size, despite the 
      absence of HIF-1. Tumor size was not further increased in cells with 
      reconstituted HIF-1 activity, indicating that the effects of Akt on tumorigenesis 
      were not limited by the absence of HIF-1. Increased tumor size in Akt-expressing, 
      HIF-deficient cells was associated with vascular endothelial growth factor 
      secretion and tumor vascularization. In addition to vascular endothelial growth 
      factor production, Akt also conferred a cell-autonomous competitive advantage to 
      tumor cells in an in vivo competition experiment. Thus, Akt has potent, 
      HIF-1-independent oncogenic and angiogenic activities.
FAU - Arsham, Andrew M
AU  - Arsham AM
AD  - Committee on Genetics, University of Chicago, Chicago, Illinois, USA.
FAU - Plas, David R
AU  - Plas DR
FAU - Thompson, Craig B
AU  - Thompson CB
FAU - Simon, M Celeste
AU  - Simon MC
LA  - eng
GR  - CA66310/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Cell Division
MH  - DNA-Binding Proteins/deficiency/*physiology
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Liver Neoplasms, Experimental/*blood supply/genetics/metabolism/*pathology
MH  - Mice
MH  - Mice, Nude
MH  - Neovascularization, Pathologic/enzymology/metabolism/*pathology
MH  - Nuclear Proteins/deficiency/*physiology
MH  - Protein Serine-Threonine Kinases/biosynthesis/genetics/*physiology
MH  - Proto-Oncogene Proteins/biosynthesis/genetics/*physiology
MH  - Proto-Oncogene Proteins c-akt
MH  - *Transcription Factors
MH  - Vascular Endothelial Growth Factor A/biosynthesis
EDAT- 2004/05/20 05:00
MHDA- 2004/08/03 05:00
CRDT- 2004/05/20 05:00
PHST- 2004/05/20 05:00 [pubmed]
PHST- 2004/08/03 05:00 [medline]
PHST- 2004/05/20 05:00 [entrez]
AID - 64/10/3500 [pii]
AID - 10.1158/0008-5472.CAN-03-2239 [doi]
PST - ppublish
SO  - Cancer Res. 2004 May 15;64(10):3500-7. doi: 10.1158/0008-5472.CAN-03-2239.