Tumor-suppressive activity of the cell death activator GRIM-19 on a constitutively active signal transducer and activator of transcription 3.
Cancer Res
; 67(13): 6212-20, 2007 Jul 01.
Article
in En
| MEDLINE
| ID: mdl-17616678
ABSTRACT
Signal transducers and activators of transcription 3 (STAT3) was originally identified as a transcription factor that mediates cytokine-induced responses. In these pathways, Janus-activated kinase (JAK)-induced transient tyrosine phosphorylation of STAT3 promotes gene expression in response to a number of cytokines, which is inhibited by feedback mechanisms. A number of studies have shown that STAT3 is constitutively activated in human cancer cells, leading to cell proliferation. It is unclear, apart from a chronic tyrosyl phosphorylation of STAT3, what mechanisms contribute to the STAT3 deregulation in tumors. Earlier, we have isolated a novel growth inhibitory gene product, gene associated with retinoid-IFN-induced mortality 19 (GRIM-19), using a genetic approach. GRIM-19 is an IFN/retinoic acid-regulated growth suppressor. Subsequent analyses have shown that GRIM-19 binds to STAT3 and prevents interleukin-6-induced transcription of cellular genes. However, its effects on a constitutively active STAT3 and cellular transformation are unknown. In this study, we show that GRIM-19 suppresses constitutive STAT3-induced cellular transformation in vitro and in vivo by down-regulating the expression of a number of cellular genes involved in cell proliferation and apoptosis.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Expression Regulation, Neoplastic
/
STAT3 Transcription Factor
/
Apoptosis Regulatory Proteins
/
NADH, NADPH Oxidoreductases
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Cancer Res
Year:
2007
Type:
Article
Affiliation country:
United States