PMID- 12124175
OWN - NLM
STAT- MEDLINE
DCOM- 20020927
LR  - 20220317
IS  - 1535-6108 (Print)
IS  - 1535-6108 (Linking)
VI  - 1
IP  - 5
DP  - 2002 Jun
TI  - HIF activation identifies early lesions in VHL kidneys: evidence for 
      site-specific tumor suppressor function in the nephron.
PG  - 459-68
AB  - Mutations in the von Hippel-Lindau (VHL) gene are associated with hereditary and 
      sporadic clear cell renal carcinoma. VHL acts in a ubiquitin ligase complex 
      regulating hypoxia-inducible factor-1 (HIF-1), but the link between this function 
      and cancer development is unclear. Here we show that in the kidneys of patients 
      with VHL disease, HIF activation is an early event occurring in morphologically 
      normal single cells within the renal tubules. In comparison, dysplastic lesions, 
      cystic lesions, and tumors showed evidence of additional mechanisms that amplify 
      HIF activation. Detection of cells with constitutive HIF activation identified a 
      large number of previously unrecognized foci of VHL inactivation. In proximal 
      tubules these were almost entirely unicellular, whereas multicellular foci were 
      almost exclusively seen in the distal nephron.
FAU - Mandriota, Stefano J
AU  - Mandriota SJ
AD  - Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, United Kingdom.
FAU - Turner, Kevin J
AU  - Turner KJ
FAU - Davies, David R
AU  - Davies DR
FAU - Murray, Paul G
AU  - Murray PG
FAU - Morgan, Neil V
AU  - Morgan NV
FAU - Sowter, Heidi M
AU  - Sowter HM
FAU - Wykoff, Charles C
AU  - Wykoff CC
FAU - Maher, Eamonn R
AU  - Maher ER
FAU - Harris, Adrian L
AU  - Harris AL
FAU - Ratcliffe, Peter J
AU  - Ratcliffe PJ
FAU - Maxwell, Patrick H
AU  - Maxwell PH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Cell
JT  - Cancer cell
JID - 101130617
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Monosaccharide Transport Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA Probes)
RN  - 0 (SLC2A1 protein, human)
RN  - 0 (Transcription Factors)
RN  - EC 4.2.1.1 (CA9 protein, human)
RN  - EC 4.2.1.1 (Carbonic Anhydrase IX)
RN  - EC 4.2.1.1 (Carbonic Anhydrases)
SB  - IM
MH  - Adenocarcinoma, Clear Cell/genetics/*metabolism/pathology
MH  - Adult
MH  - Antigens, CD/metabolism
MH  - *Antigens, Neoplasm
MH  - Apoptosis/physiology
MH  - Carbonic Anhydrase IX
MH  - Carbonic Anhydrases/metabolism
MH  - Carcinoma, Renal Cell/genetics/*metabolism/pathology
MH  - DNA-Binding Proteins/*metabolism
MH  - Genes, Tumor Suppressor/*physiology
MH  - Glucose Transporter Type 1
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Immunoenzyme Techniques
MH  - In Situ Hybridization
MH  - In Situ Nick-End Labeling
MH  - Kidney Neoplasms/genetics/*metabolism/pathology
MH  - Middle Aged
MH  - Monosaccharide Transport Proteins/metabolism
MH  - Neoplasm Proteins/metabolism
MH  - Nephrectomy
MH  - Nephrons/*metabolism
MH  - Nuclear Proteins/*metabolism
MH  - RNA Probes
MH  - *Transcription Factors
MH  - von Hippel-Lindau Disease/genetics/*metabolism/pathology
EDAT- 2002/07/19 10:00
MHDA- 2002/09/28 04:00
CRDT- 2002/07/19 10:00
PHST- 2002/07/19 10:00 [pubmed]
PHST- 2002/09/28 04:00 [medline]
PHST- 2002/07/19 10:00 [entrez]
AID - S1535610802000715 [pii]
AID - 10.1016/s1535-6108(02)00071-5 [doi]
PST - ppublish
SO  - Cancer Cell. 2002 Jun;1(5):459-68. doi: 10.1016/s1535-6108(02)00071-5.