PMID- 11156414
OWN - NLM
STAT- MEDLINE
DCOM- 20010222
LR  - 20230307
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 60
IP  - 24
DP  - 2000 Dec 15
TI  - Hypoxia-inducible expression of tumor-associated carbonic anhydrases.
PG  - 7075-83
AB  - The transcriptional complex hypoxia-inducible factor-1 (HIF-1) has emerged as an 
      important mediator of gene expression patterns in tumors, although the range of 
      responding genes is still incompletely defined. Here we show that the 
      tumor-associated carbonic anhydrases (CAs) are tightly regulated by this system. 
      Both CA9 and CA12 were strongly induced by hypoxia in a range of tumor cell 
      lines. In renal carcinoma cells that are defective for the von Hippel-Lindau 
      (VHL) tumor suppressor, up-regulation of these CAs is associated with loss of 
      regulation by hypoxia, consistent with the critical function of pVHL in the 
      regulation of HIF-1. Further studies of CA9 defined a HIF-1-dependent hypoxia 
      response element in the minimal promoter and demonstrated that tight regulation 
      by the HIF/pVHL system was reflected in the pattern of CA IX expression within 
      tumors. Generalized up-regulation of CA IX in VHL-associated renal cell carcinoma 
      contrasted with focal perinecrotic expression in a variety of non-VHL-associated 
      tumors. In comparison with vascular endothelial growth factor mRNA, expression of 
      CA IX demonstrated a similar, although more tightly circumscribed, pattern of 
      expression around regions of necrosis and showed substantial although incomplete 
      overlap with activation of the hypoxia marker pimonidazole. These studies define 
      a new class of HIF-1-responsive gene, the activation of which has implications 
      for the understanding of hypoxic tumor metabolism and which may provide 
      endogenous markers for tumor hypoxia.
FAU - Wykoff, C C
AU  - Wykoff CC
AD  - Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
FAU - Beasley, N J
AU  - Beasley NJ
FAU - Watson, P H
AU  - Watson PH
FAU - Turner, K J
AU  - Turner KJ
FAU - Pastorek, J
AU  - Pastorek J
FAU - Sibtain, A
AU  - Sibtain A
FAU - Wilson, G D
AU  - Wilson GD
FAU - Turley, H
AU  - Turley H
FAU - Talks, K L
AU  - Talks KL
FAU - Maxwell, P H
AU  - Maxwell PH
FAU - Pugh, C W
AU  - Pugh CW
FAU - Ratcliffe, P J
AU  - Ratcliffe PJ
FAU - Harris, A L
AU  - Harris AL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Lymphokines)
RN  - 0 (Nitroimidazoles)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Radiation-Sensitizing Agents)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - 46JO4D76R2 (pimonidazole)
RN  - 63231-63-0 (RNA)
RN  - EC 4.2.1.1 (Carbonic Anhydrases)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Blotting, Western
MH  - Carbonic Anhydrases/biosynthesis/*metabolism
MH  - Carcinoma/metabolism
MH  - Carcinoma, Renal Cell/genetics/metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - Endothelial Growth Factors/metabolism
MH  - Genes, Reporter
MH  - Humans
MH  - *Hypoxia
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Immunoblotting
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Kidney Neoplasms/metabolism
MH  - Lymphokines/metabolism
MH  - Models, Genetic
MH  - Necrosis
MH  - Nitroimidazoles/pharmacology
MH  - Nuclear Proteins/*metabolism
MH  - Oxygen/metabolism
MH  - Plasmids/metabolism
MH  - Promoter Regions, Genetic
MH  - RNA/metabolism
MH  - RNA, Messenger/metabolism
MH  - Radiation-Sensitizing Agents/pharmacology
MH  - Skin Neoplasms/metabolism
MH  - *Transcription Factors
MH  - Tumor Cells, Cultured
MH  - Up-Regulation
MH  - Urinary Bladder Neoplasms/metabolism
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 2001/01/13 11:00
MHDA- 2001/03/03 10:01
CRDT- 2001/01/13 11:00
PHST- 2001/01/13 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2001/01/13 11:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2000 Dec 15;60(24):7075-83.