PMID- 14996738
OWN - NLM
STAT- MEDLINE
DCOM- 20040331
LR  - 20220409
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 64
IP  - 5
DP  - 2004 Mar 1
TI  - Hypoxia-inducible factor-1-independent regulation of vascular endothelial growth 
      factor by hypoxia in colon cancer.
PG  - 1765-72
AB  - The induction of vascular endothelial growth factor (VEGF) is an essential 
      feature of tumor angiogenesis, and the hypoxia-inducible factor-1 (HIF-1) 
      transcription factor is known to be a key mediator of this process. In colon 
      cancer, the frequently mutated K-ras oncogene also can regulate VEGF expression, 
      but the role that K-ras may play in hypoxia is unknown. Hypoxia induced VEGF 
      promoter activity, mRNA, and protein levels in colon cancer cells. Although 
      HIF-1alpha was induced by hypoxia, VEGF reporter constructs with selectively 
      mutated hypoxia-response elements remained responsive to hypoxia. In addition, 
      "knockdown" of HIF-1alpha by RNA interference only minimally inhibited the 
      hypoxic induction of VEGF. A region of the VEGF promoter between -420 and -90 bp 
      mediated this HIF-independent induction by hypoxia. The introduction of 
      K-ras(Val12) augmented the hypoxic induction of VEGF, and this was observed in 
      wild-type and HIF-1alpha knockdown colon cancer cells. Thus, VEGF may be induced 
      by hypoxia through HIF-dependent and HIF-independent pathways, and K-ras also can 
      induce VEGF in hypoxia independent of HIF-1. These findings suggest the existence 
      of multiple mechanisms regulating the hypoxic induction of VEGF in colon cancer.
FAU - Mizukami, Yusuke
AU  - Mizukami Y
AD  - Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital and 
      Harvard Medical School, Boston, Massachusetts 02114, USA.
FAU - Li, Jingnan
AU  - Li J
FAU - Zhang, Xiaobo
AU  - Zhang X
FAU - Zimmer, Michael A
AU  - Zimmer MA
FAU - Iliopoulos, Othon
AU  - Iliopoulos O
FAU - Chung, Daniel C
AU  - Chung DC
LA  - eng
GR  - CA92594/CA/NCI NIH HHS/United States
PT  - Journal Article
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, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - *Cell Hypoxia
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/*blood supply
MH  - DNA-Binding Proteins/*physiology
MH  - *Gene Expression Regulation, Neoplastic
MH  - Genes, ras
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Neovascularization, Pathologic/etiology
MH  - Nuclear Proteins/*physiology
MH  - Promoter Regions, Genetic
MH  - *Transcription Factors
MH  - Vascular Endothelial Growth Factor A/*genetics
EDAT- 2004/03/05 05:00
MHDA- 2004/04/01 05:00
CRDT- 2004/03/05 05:00
PHST- 2004/03/05 05:00 [pubmed]
PHST- 2004/04/01 05:00 [medline]
PHST- 2004/03/05 05:00 [entrez]
AID - 10.1158/0008-5472.can-03-3017 [doi]
PST - ppublish
SO  - Cancer Res. 2004 Mar 1;64(5):1765-72. doi: 10.1158/0008-5472.can-03-3017.