PMID- 11059752
OWN - NLM
STAT- MEDLINE
DCOM- 20001108
LR  - 20081121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 60
IP  - 20
DP  - 2000 Oct 15
TI  - Hyperinducibility of hypoxia-responsive genes without p53/p21-dependent 
      checkpoint in aggressive prostate cancer.
PG  - 5630-4
AB  - Hypoxia limits tumor growth but selects for higher metastatic potential. We 
      tested the functional activity of hypoxia-inducible factor-1 (HIF-1) in prostate 
      cell lines ranging from normal epithelial cells (PrEC), hormone-dependent LNCaP, 
      hormone-independent DU145, PC-3 to highly metastatic PC-3M cancer cell lines. We 
      found that HIF-1-stimulated transcription was the lowest in PrEC and LNCaP cells 
      and the highest in PC-3M cells. The induction by hypoxia of the HIF-1 dependent 
      genes Cap43 and GAPDH was the highest in the most aggressive PC-3M cancer cells. 
      Because these advanced prostate cancer cell lines have lost p53 function, this 
      further shifts a balance from p53 to HIF-1 transcriptional regulation, and a high 
      ratio of HIF-1-dependent:p53-dependent transcription was a marker of the advanced 
      malignant phenotype. Transient transfection of HIF-1alpha expression vector 
      induced transcription from p21 promoter construct in prostate cancer cell lines. 
      Furthermore, hypoxia slightly induced p21 mRNA in these cells. However, neither 
      expression of p21 nor hypoxia caused growth arrest in PC-3M cells. Therefore, 
      high inducibility of HIF-1-dependent genes, loss of p53 functions with high ratio 
      of HIF-1-dependent:p53-dependent transcription, and loss of sensitivity to p21 
      inhibition is a part of hypoxic phenotype associated with aggressive cancer 
      behavior.
FAU - Salnikow, K
AU  - Salnikow K
AD  - Nelson Institute of Environmental Medicine, and Kaplan Comprehensive Cancer 
      Center, New York University School of Medicine, New York 10016, USA. 
      salnikow@env.med.nyu.edu
FAU - Costa, M
AU  - Costa M
FAU - Figg, W D
AU  - Figg WD
FAU - Blagosklonny, M V
AU  - Blagosklonny MV
LA  - eng
GR  - CA16087/CA/NCI NIH HHS/United States
GR  - ES00260/ES/NIEHS NIH HHS/United States
GR  - ES05512/ES/NIEHS NIH HHS/United States
PT  - Comparative Study
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 (CDKN1A protein, human)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
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 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (N-myc downstream-regulated gene 1 protein)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
SB  - IM
MH  - Cell Cycle/genetics
MH  - Cell Cycle Proteins
MH  - Cell Hypoxia/genetics
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclins/biosynthesis/genetics/*physiology
MH  - DNA-Binding Proteins/biosynthesis/*genetics/physiology
MH  - Flow Cytometry
MH  - Gene Expression Regulation, Neoplastic
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/genetics
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Intracellular Signaling Peptides and Proteins
MH  - Male
MH  - Neoplasm Metastasis
MH  - Nuclear Proteins/biosynthesis/*genetics/physiology
MH  - Promoter Regions, Genetic/genetics
MH  - Prostatic Neoplasms/*genetics/metabolism/pathology
MH  - Protein Biosynthesis
MH  - Proteins/genetics
MH  - Transcription Factors/biosynthesis/*genetics/physiology
MH  - Transcription, Genetic/physiology
MH  - Transcriptional Activation/genetics
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/biosynthesis/genetics/*physiology
EDAT- 2000/11/04 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/11/04 11:00
PHST- 2000/11/04 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/04 11:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2000 Oct 15;60(20):5630-4.