Document Detail

Inhibition of AP-1 by SARI negatively regulates transformation progression mediated by CCN1.
MedLine Citation:
PMID:  20531301     Owner:  NLM     Status:  MEDLINE    
Enhanced expression of the CCN family of secretory integrin-binding proteins correlates with many essential components of the cancerous state, including tumor cell adhesion, proliferation, invasion and migration. Consequently, CCN1 expression is elevated in various cancers, including breast cancer, and its expression directly correlates with poor patient prognosis. Using subtraction-hybridization, combined with induction of cancer cell terminal differentiation, we cloned SARI (suppressor of activator protein (AP)-1, regulated by interferon (IFN)), an IFN-beta-inducible, potent tumor suppressor gene that exerts cancer-selective growth inhibitory effects. Forced expression of SARI using an adenovirus (Ad.SARI) inhibits AP-1 function and downregulates CCN1 expression in multiple cancer lineages, resulting in a profound inhibition in anchorage-independent cell growth and tumor cell invasion. Overexpression of SARI reduces CCN1-promoter activity through inhibition of AP-1 binding. Accordingly, SARI selectively blocks expression of the transformed state in rat embryo fibroblast cells that stably overexpress c-Jun. These results illustrate that SARI inhibits AP-1 transactivating factor binding to the cis-element of the CCN1 promoter, possibly through its interaction with c-Jun. Overall, SARI can directly inhibit CCN1-induced transformation by inhibiting the transcription of CCN1, as well as indirectly by inhibiting the expression of c-Jun (and hence blocking AP-1 activity). In these contexts, transformed cells 'addicted' to AP-1 activity are rendered susceptible to SARI-mediated inhibition of expression of the transformed phenotype.
R Dash; Z-Z Su; S-G Lee; B Azab; H Boukerche; D Sarkar; P B Fisher
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-06-07
Journal Detail:
Title:  Oncogene     Volume:  29     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-05     Completed Date:  2010-09-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  4412-23     Citation Subset:  IM    
Department of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Cell Adhesion / genetics
Cell Proliferation
Cell Transformation, Neoplastic / genetics*
Cysteine-Rich Protein 61 / physiology*
Disease Progression
Genes, Tumor Suppressor / physiology*
Mice, Nude
Neoplasm Invasiveness
Transcription Factor AP-1 / antagonists & inhibitors*
Tumor Cells, Cultured
Tumor Suppressor Proteins / genetics,  physiology*
Validation Studies as Topic
Xenograft Model Antitumor Assays
Grant Support
P01 CA104177/CA/NCI NIH HHS; R01 CA097318/CA/NCI NIH HHS
Reg. No./Substance:
0/Cysteine-Rich Protein 61; 0/Transcription Factor AP-1; 0/Tumor Suppressor Proteins

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

Previous Document:  New insights into apoptosis signaling by Apo2L/TRAIL.
Next Document:  Global analysis of CpG methylation reveals epigenetic control of the radiosensitivity in lung cancer...