Document Detail


Caspase-3 inhibits the growth of breast cancer cells independent of protease activity.
MedLine Citation:
PMID:  15316934     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this study, the MCF-7 breast cancer cells that lack caspase-3 were transfected with a wild type (WT) or mutant caspase-3 cDNA. Expression of the WT, but not of the mutant, caspase-3 was associated with increased caspase activity and susceptibility to staurosporine (STS)-induced apoptosis. Both derivatives displayed inhibition of cell growth compared with vector control cells. Growth inhibition was associated with increased expression of the cyclin dependent kinase (CDK) inhibitor p27Kip1 in the WT, but not in the mutant caspase-3 expressing cells. Cyclin D1 expression level was not affected by caspase-3 expression. Phosphorylation of the Akt protein was decreased in both WT and mutant caspase transfected cells, although Akt expression level remained unchanged. These results suggest that caspase-3 might have biological functions independent of its protease activity and that its loss might contribute to tumor development by increasing the growth potential of cancer cells.
Authors:
Beatrice Faraglia; Alessia Bonsignore; Franco Scaldaferri; Alma Boninsegna; Achille Cittadini; Cesare Mancuso; Alessandro Sgambato
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  202     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2004-11-30     Completed Date:  2005-02-18     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  478-82     Citation Subset:  IM    
Copyright Information:
2004 Wiley-Liss, Inc.
Affiliation:
Istituto di Patologia Generale, Centro di Ricerche Oncologiche Giovanni XXIII, Rome, Italy.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Breast Neoplasms / enzymology*,  pathology*
Caspase 3
Caspases / pharmacology*
Cell Cycle Proteins / metabolism
Cell Division / drug effects
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p27
Cyclin-Dependent Kinases / antagonists & inhibitors
Enzyme Inhibitors / metabolism
Female
Humans
Phosphorylation / drug effects
Protein-Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-akt
Rats
Staurosporine / pharmacology
Transfection
Tumor Suppressor Proteins / metabolism
Chemical
Reg. No./Substance:
0/Cdkn1b protein, rat; 0/Cell Cycle Proteins; 0/Enzyme Inhibitors; 0/Proto-Oncogene Proteins; 0/Tumor Suppressor Proteins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 62996-74-1/Staurosporine; EC 2.7.1.37/AKT1 protein, human; EC 2.7.1.37/Akt1 protein, rat; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.22/Cyclin-Dependent Kinases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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


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