Hypoxia Up-regulates HIF Expression While Suppressing Cell Growth and NOTCH Activity in Leukaemia Cells.
Basic Helix-Loop-Helix Transcription Factors
/ genetics
Cell Cycle
/ genetics
Cell Hypoxia
/ genetics
Cell Line, Tumor
Cell Proliferation
/ genetics
Gene Expression Regulation, Leukemic
/ genetics
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
/ genetics
Leukemia
/ genetics
NF-kappa B
/ genetics
Phosphorylation
Proto-Oncogene Proteins c-akt
/ genetics
Receptor, Notch1
/ genetics
Signal Transduction
/ genetics
TOR Serine-Threonine Kinases
/ genetics
HIF
NOTCH
hypoxia
leukaemia
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
received:
22
05
2019
revised:
18
06
2019
accepted:
20
06
2019
entrez:
2
8
2019
pubmed:
2
8
2019
medline:
8
8
2019
Statut:
ppublish
Résumé
To examine the influence of hypoxia on the in vitro growth of leukaemia cells and the activity of signalling proteins to better understand the pathophysiology of leukaemia cells in human bone marrow. Six human leukaemia cell lines were cultured under normoxic or hypoxic conditions. Cell growth, recovery of clonogenic cells, and the expression and activation of various signalling proteins were examined. Hypoxia suppressed cell growth and the recovery of clonogenic cells. Moreover, hypoxia up-regulated hypoxia-inducible factor (HIF) 1α and HIF2α expression while suppressing the expression and activation of NOTCH1, mechanistic target of rapamycin kinase (mTOR) activation, and nuclear factor-kappa B (NF-κB) phosphorylation. We found that hypoxia up-regulated HIF expression while it suppressed the self-renewal capacity of leukaemia cells, NOTCH activity, and expression of its down-stream signalling molecules, which differs from previous reports mentioning that HIF activates NOTCH signalling. Our findings serve to further elucidate the in vivo pathophysiology of leukaemia cells.
Identifiants
pubmed: 31366501
pii: 39/8/4165
doi: 10.21873/anticanres.13575
doi:
Substances chimiques
Basic Helix-Loop-Helix Transcription Factors
0
HIF1A protein, human
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
NF-kappa B
0
NOTCH1 protein, human
0
Receptor, Notch1
0
endothelial PAS domain-containing protein 1
1B37H0967P
MTOR protein, human
EC 2.7.1.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4165-4170Informations de copyright
Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.