PMID- 10934146
OWN - NLM
STAT- MEDLINE
DCOM- 20000823
LR  - 20220225
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 157
IP  - 2
DP  - 2000 Aug
TI  - The expression and distribution of the hypoxia-inducible factors HIF-1alpha and 
      HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages.
PG  - 411-21
AB  - The cellular response to hypoxia includes the hypoxia-inducible factor-1 
      (HIF-1)-induced transcription of genes involved in diverse processes such as 
      glycolysis and angiogenesis. Induction of the HIF-regulated genes, as a 
      consequence of the microenvironment or genetic changes, is known to have an 
      important role in the growth of experimental tumors. Hypoxia-inducible factors 
      1alpha and 2alpha (HIF-1alpha and HIF-2alpha) are known to dimerize with the aryl 
      hydrocarbon receptor nuclear translocator in mediating this response. Because 
      regulation of the alpha chain protein level is a primary determinant of HIF 
      activity, our aim was to investigate the distribution of HIF-1alpha and 
      HIF-2alpha by immunohistochemistry in normal and pathological tissues using 
      monoclonal antibodies (mAb). We raised a new mAb to detect HIF-1alpha, designated 
      122, and used our previously validated mAb 190b to HIF-2alpha. In the majority of 
      solid tumors examined, including bladder, brain, breast, colon, ovarian, 
      pancreatic, prostate, and renal carcinomas, nuclear expression of HIF-1alpha and 
      -2alpha was observed in varying subsets of the tumor cells. HIF-2alpha was also 
      strongly expressed by subsets of tumor-associated macrophages, sometimes in the 
      absence of any tumor cell expression. Less frequently staining was observed in 
      other stromal cells within the tumors and in normal tissue adjacent to tumor 
      margins. In contrast, in normal tissue neither molecule was detectable except 
      within subsets of bone marrow macrophages, where HIF-2alpha was strongly 
      expressed.
FAU - Talks, K L
AU  - Talks KL
AD  - Nuffield Department of Clinical Laboratory Sciences, University of Oxford, United 
      Kingdom.
FAU - Turley, H
AU  - Turley H
FAU - Gatter, K C
AU  - Gatter KC
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
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
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 (RNA, Messenger)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 1B37H0967P (endothelial PAS domain-containing protein 1)
SB  - IM
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors
MH  - Blotting, Western
MH  - COS Cells
MH  - Cell Line
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Macrophages/*chemistry/metabolism/pathology
MH  - Neoplasms/genetics/*metabolism/pathology
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Paraffin Embedding
MH  - RNA, Messenger/genetics/metabolism
MH  - Tissue Distribution
MH  - *Trans-Activators
MH  - *Transcription Factors
MH  - Tumor Cells, Cultured
PMC - PMC1850121
EDAT- 2000/08/10 11:00
MHDA- 2000/08/29 11:01
PMCR- 2001/02/01
CRDT- 2000/08/10 11:00
PHST- 2000/08/10 11:00 [pubmed]
PHST- 2000/08/29 11:01 [medline]
PHST- 2000/08/10 11:00 [entrez]
PHST- 2001/02/01 00:00 [pmc-release]
AID - S0002-9440(10)64554-3 [pii]
AID - 2297 [pii]
AID - 10.1016/s0002-9440(10)64554-3 [doi]
PST - ppublish
SO  - Am J Pathol. 2000 Aug;157(2):411-21. doi: 10.1016/s0002-9440(10)64554-3.