Document Detail

Interruption of NFkappaB-STAT1 signaling mediates EGF-induced cell-cycle arrest.
MedLine Citation:
PMID:  10825242     Owner:  NLM     Status:  MEDLINE    
It is known that EGF induces the cell-cycle arrest in A431 cells that possess high numbers of EGF receptors and it was previously suggested that p21/WAF1 protein was a major effector molecule of the EGF-mediated cell-cycle arrest of A431 cells. Here, we further investigate this phenomenon using the decoy double-strand oligonucleotides for STAT-binding sequence (STAT decoy) and IkappaB, an inhibitor of the nuclear factor kappa B (NFkappaB). Addition of STAT decoy restored EGF-induced A431 cell-growth arrest. Interestingly, infection of adenovirus vectors to express IkappaB (AxIkappaBalphaDeltaN) as the inhibitor of NFkappaB also reversed the A431 cell-growth inhibition. The individual treatment of two inhibitors partially inhibited the WAF1 gene expression, whereas simultaneous treatment of two inhibitors exhibited more efficient inhibition. These observations suggest the activation of NFkappaB via IkappaB degradation and STAT1 via specific receptor kinase activity synergistically induce WAF1 gene expression in A431 cells. Thus, NFkappaB and STAT1 pathways mutually interact to play an important role in the EGF-induced intracellular reaction.
M Ohtsubo; A Takayanagi; S Gamou; N Shimizu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  184     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2000 Jul 
Date Detail:
Created Date:  2000-07-03     Completed Date:  2000-07-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  131-7     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Wiley-Liss, Inc.
Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan.
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MeSH Terms
Carcinoma, Squamous Cell
Cell Cycle / drug effects,  physiology*
Cell Division
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / genetics,  metabolism
DNA-Binding Proteins / genetics,  metabolism*,  physiology
Enzyme Inhibitors / metabolism
Epidermal Growth Factor / pharmacology*
Genes, Reporter
I-kappa B Proteins*
NF-kappa B / metabolism*
STAT1 Transcription Factor
Signal Transduction*
Trans-Activators / metabolism*
Tumor Cells, Cultured
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/DNA-Binding Proteins; 0/Enzyme Inhibitors; 0/I-kappa B Proteins; 0/NF-kappa B; 0/STAT1 Transcription Factor; 0/STAT1 protein, human; 0/Trans-Activators; 139874-52-5/NF-kappaB inhibitor alpha; 62229-50-9/Epidermal Growth Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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