Document Detail


Role of extracellular matrix in regulation of staurosporine-induced apoptosis in breast cancer cells.
MedLine Citation:
PMID:  15756452     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Autocrine and paracrine mechanisms modulate the synthesis and secretion of extracellular matrix (ECM); moreover, each component of the ECM is capable of modulating the synthesis and release of other ECM molecules. Therefore, the synthesis of ECM glycoprotein fibronectin and laminin was studied in the human breast cancer cell lines MCF7 and MDA MB 23, plated on different ECM. Our results showed that the cells plated on a fibronectin substrate increased laminin synthesis: this event correlated with an increase in alpha2 and alpha3 integrin subunits. Staurosporine-induced apoptosis was then analyzed in the cell lines plated on different ECM. Staurosporine treatment determined the apoptosis of 35 and 33% respectively of MDA MB 231 and MCF7; these values increased to 60 and 64% in cells plated on laminin, to 48 and 63% in cells plated on fibronectin and to 64 and 69% in cells plated on matrigel. Moreover, staurosporine treatment decreased bcl-2 expression in the cells plated on fibronectin and laminin. Yet, staurosporine treatment determined PARP cleavage and PARP partial disappearance when the cells were plated on matrigel. Finally, a partial loss of function mutant Ras protein that activated only Raf pathway, was expressed in MCF7, in order to identify whether the increase of apoptosis induced by extracellular matrix involved the Raf/MAP kinase pathway. The increase of apoptosis of the cells plated on matrigel suggested that the activation of the Raf pathway is probably involved in the decrease of survival on matrigel. These data demonstrate that the modification of ECM modulates the apoptotic process of breast cancer cells and suggest that it is worthwhile to dissect the role of ECM in the control of apoptotic process.
Authors:
F Vasaturo; C Malacrino; E Sallusti; G Coppotelli; P Birarelli; A Giuffrida; L Albonici; L Simonelli; A Modesti; M Modesti; S Scarpa
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Oncology reports     Volume:  13     ISSN:  1021-335X     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-03-09     Completed Date:  2005-08-26     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  745-50     Citation Subset:  IM    
Affiliation:
Department of Experimental Medicine and Pathology, University of Rome La Sapienza, viale Regina Elena 324, 00161 Rome, Italy.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis*
Blotting, Western
Breast Neoplasms / metabolism*,  pathology
Cell Death
Cell Line, Tumor
Cell Separation
Collagen / pharmacology
Drug Combinations
Enzyme Inhibitors / pharmacology*
Extracellular Matrix / metabolism*
Fibronectins / biosynthesis,  chemistry
Flow Cytometry
Humans
Immunoprecipitation
Laminin / biosynthesis,  chemistry,  metabolism,  pharmacology
Poly(ADP-ribose) Polymerases / metabolism
Polylysine / chemistry
Proteoglycans / pharmacology
Proto-Oncogene Proteins c-bcl-2 / metabolism
Staurosporine / pharmacology*
Transfection
Tumor Suppressor Protein p53 / metabolism
bcl-2-Associated X Protein
Chemical
Reg. No./Substance:
0/Drug Combinations; 0/Enzyme Inhibitors; 0/Fibronectins; 0/Laminin; 0/Proteoglycans; 0/Proto-Oncogene Proteins c-bcl-2; 0/Tumor Suppressor Protein p53; 0/bcl-2-Associated X Protein; 119978-18-6/matrigel; 25104-18-1/Polylysine; 62996-74-1/Staurosporine; 9007-34-5/Collagen; EC 2.4.2.30/Poly(ADP-ribose) Polymerases

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