Document Detail

Repression of PTEN phosphatase by Snail1 transcriptional factor during gamma radiation-induced apoptosis.
MedLine Citation:
PMID:  18172008     Owner:  NLM     Status:  MEDLINE    
The product of the Snail1 gene is a transcriptional repressor required for triggering the epithelial-to-mesenchymal transition. Furthermore, ectopic expression of Snail1 in epithelial cells promotes resistance to apoptosis. In this study, we demonstrate that this resistance to gamma radiation-induced apoptosis caused by Snail1 is associated with the inhibition of PTEN phosphatase. In MDCK cells, mRNA levels of the p53 target gene PTEN are induced after gamma radiation; the transfection of Snail1 prevents this up-regulation. Decreased mRNA levels of PTEN were also detected in RWP-1 cells after the ectopic expression of this transcriptional factor. Snail1 represses and associates to the PTEN promoter as detected both by the electrophoretic mobility shift assay and chromatin immunoprecipitation experiments performed with either endogenous or ectopic Snail1. The binding of Snail1 to the PTEN promoter increases after gamma radiation, correlating with the stabilization of Snail1 protein, and prevents the association of p53 to the PTEN promoter. These results stress the critical role of Snail1 in the control of apoptosis and demonstrate the regulation of PTEN phosphatase by this transcriptional repressor.
Maria Escrivà; Sandra Peiró; Nicolás Herranz; Patricia Villagrasa; Natàlia Dave; Bàrbara Montserrat-Sentís; Stephen A Murray; Clara Francí; Thomas Gridley; Ismo Virtanen; Antonio García de Herreros
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-01-02
Journal Detail:
Title:  Molecular and cellular biology     Volume:  28     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-02-15     Completed Date:  2008-03-17     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1528-40     Citation Subset:  IM    
Institut Municipal d'Investigació Mèdica, Parc de Recerca Biomèdica de Barcelona, c/Dr. Aiguader 88, E-08003 Barcelona, Spain.
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MeSH Terms
Apoptosis / radiation effects*
Cell Line
Cell Line, Tumor
Chromatin Immunoprecipitation
DNA Damage
DNA, Complementary
G2 Phase
Gamma Rays*
Gene Expression Regulation*
Genes, Reporter
Luciferases, Firefly / analysis,  metabolism
Luciferases, Renilla / analysis,  metabolism
Luminescent Agents / metabolism
PTEN Phosphohydrolase / antagonists & inhibitors*
Pancreatic Neoplasms / pathology
Promoter Regions, Genetic
Protein Synthesis Inhibitors / pharmacology
Proto-Oncogene Proteins c-akt / metabolism
Puromycin / pharmacology
RNA, Messenger / metabolism
RNA, Small Interfering / pharmacology
Selection, Genetic
Time Factors
Transcription Factors / genetics,  metabolism*,  pharmacology
Grant Support
Reg. No./Substance:
0/DNA, Complementary; 0/Luminescent Agents; 0/Protein Synthesis Inhibitors; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Transcription Factors; 0/snail family transcription factors; 53-79-2/Puromycin; EC, Renilla; EC, Firefly; EC Proteins c-akt; EC Phosphohydrolase

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