Document Detail

Activation of Stat3 by cell confluence reveals negative regulation of Stat3 by cdk2.
MedLine Citation:
PMID:  12789269     Owner:  NLM     Status:  MEDLINE    
The signal transducing protein Stat3 activates gene transcription in cells in response to multiple cytokines. Constitutive activation of Stat3 has been observed in solid tumors including head and neck squamous cell carcinoma. Stat3 activation in cancer has been associated with autocrine stimulatory loops and is believed to convey a growth advantage to cells. We now demonstrate ligand-independent activation of Stat3 by high cell density in multiple cancer cell lines. Activation of Stat3 is associated with antiproliferative rather than proliferative conditions. Interference with cdk2 activity upregulates Stat3 phosphorylation and Stat3-directed DNA-binding activity. Our data supports a model in which Stat3 activity is partially suppressed by cdk2 in growing cells and derepressed upon cell confluence.
Richard A Steinman; Abbey Wentzel; Yalin Lu; Christine Stehle; Jennifer Rubin Grandis
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Oncogene     Volume:  22     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-06-05     Completed Date:  2003-07-11     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  3608-15     Citation Subset:  IM    
Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
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MeSH Terms
3T3 Cells / cytology,  metabolism
CDC2-CDC28 Kinases*
Carcinoma, Squamous Cell / drug therapy,  metabolism*,  pathology
Cell Communication / drug effects
Cell Division / physiology
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinases / antagonists & inhibitors,  metabolism*
DNA-Binding Proteins / drug effects,  metabolism*
Enzyme Inhibitors / pharmacology
Fibroblasts / cytology,  physiology
Head and Neck Neoplasms / drug therapy,  metabolism*,  pathology
Mice, Knockout
Protein-Serine-Threonine Kinases / antagonists & inhibitors,  metabolism*
Purines / pharmacology
Receptor, Epidermal Growth Factor / genetics,  metabolism
STAT3 Transcription Factor
Signal Transduction / physiology
Trans-Activators / drug effects,  metabolism*
Transforming Growth Factor alpha / pharmacology
Tumor Cells, Cultured
rac1 GTP-Binding Protein / metabolism
Grant Support
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Enzyme Inhibitors; 0/Purines; 0/STAT3 Transcription Factor; 0/STAT3 protein, human; 0/Stat3 protein, mouse; 0/Trans-Activators; 0/Transforming Growth Factor alpha; 0/roscovitine; EC, Epidermal Growth Factor; EC Kinases; EC Kinases; EC protein, human; EC protein, mouse; EC Kinase 2; EC Kinases; EC GTP-Binding Protein

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