PMID- 12514119
OWN - NLM
STAT- MEDLINE
DCOM- 20030401
LR  - 20220331
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 17
IP  - 3
DP  - 2003 Mar
TI  - Regulation of the multidrug resistance transporter P-glycoprotein in 
      multicellular tumor spheroids by hypoxia-inducible factor (HIF-1) and reactive 
      oxygen species.
PG  - 503-5
AB  - Hypoxia in tumors is generally associated with chemoresistance and 
      radioresistance. However, the correlation between the heterodimeric 
      hypoxia-inducible factor-1 (HIF-1) and the multidrug resistance transporter 
      P-glycoprotein (P-gp) has not been investigated. Herein, we demonstrate that with 
      increasing size of DU-145 prostate multicellular tumor spheroids the pericellular 
      oxygen pressure and the generation of reactive oxygen species decreased, whereas 
      the alpha-subunit of HIF-1 (HIF-1alpha) and P-gp were up-regulated. Furthermore, 
      P-gp was up-regulated under experimental physiological hypoxia and chemical 
      hypoxia induced by either cobalt chloride or desferrioxamine. The pro-oxidants 
      H2O2 and buthionine sulfoximine down-regulated HIF-1alpha and P-gp, whereas 
      up-regulation was achieved with the radical scavengers dehydroascorbate, 
      N-acetylcysteine, and vitamin E. The correlation of HIF-1alpha and P-gp 
      expression was validated by the use of hepatoma tumor spheroids that were either 
      wild type (Hepa1) or mutant (Hepa1C4) for aryl hydrocarbon receptor nuclear 
      translocator (ARNT), i.e., HIF-1beta. Chemical hypoxia robustly increased 
      HIF-1alpha as well as P-gp expression in Hepa1 tumor spheroids, whereas no 
      changes were observed in Hepa1C4 spheroids. Hence, our data demonstrate that 
      expression of P-gp in multicellular tumor spheroids is under the control of 
      HIF-1.
FAU - Wartenberg, Maria
AU  - Wartenberg M
AD  - Department of Neurophysiology, University of Cologne, D-50931 Cologne, Germany.
FAU - Ling, Frederike C
AU  - Ling FC
FAU - Muschen, Markus
AU  - Muschen M
FAU - Klein, Florian
AU  - Klein F
FAU - Acker, Helmut
AU  - Acker H
FAU - Gassmann, Max
AU  - Gassmann M
FAU - Petrat, Kerstin
AU  - Petrat K
FAU - Putz, Volker
AU  - Putz V
FAU - Hescheler, Jurgen
AU  - Hescheler J
FAU - Sauer, Heinrich
AU  - Sauer H
LA  - eng
PT  - Journal Article
DEP - 20030102
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (ARNT protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Transcription Factors)
RN  - 138391-32-9 (Aryl Hydrocarbon Receptor Nuclear Translocator)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/*metabolism
MH  - Aryl Hydrocarbon Receptor Nuclear Translocator
MH  - Carcinoma, Hepatocellular/metabolism
MH  - Cell Hypoxia
MH  - *DNA-Binding Proteins
MH  - Drug Resistance, Multiple
MH  - Drug Resistance, Neoplasm
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Models, Biological
MH  - Mutation
MH  - Neoplasms/*metabolism/pathology
MH  - Oxidation-Reduction
MH  - Reactive Oxygen Species/*metabolism
MH  - *Receptors, Aryl Hydrocarbon
MH  - Spheroids, Cellular
MH  - Transcription Factors/genetics/metabolism/*physiology
MH  - Up-Regulation
EDAT- 2003/01/07 04:00
MHDA- 2003/04/02 05:00
CRDT- 2003/01/07 04:00
PHST- 2003/01/07 04:00 [pubmed]
PHST- 2003/04/02 05:00 [medline]
PHST- 2003/01/07 04:00 [entrez]
AID - 02-0358fje [pii]
AID - 10.1096/fj.02-0358fje [doi]
PST - ppublish
SO  - FASEB J. 2003 Mar;17(3):503-5. doi: 10.1096/fj.02-0358fje. Epub 2003 Jan 2.