Linked Life Data

20682646

Source:http://linkedlifedata.com/resource/pubmed/id/20682646

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2010-8-11
pubmed:abstractText
Constitutive activation of signal transducer and activator of transcription 3 (STAT3) is common in many human and murine cancer cells, and its activation leads to cellular transformation. STAT3 pathway inhibitors have been reported to suppress cancer growth. To investigate the antitumor effects of inhibiting the STAT3-mediated signaling cascade in the cancer microenvironment, using a molecular-targeting approach, we focused on the gene associated with retinoid-IFN-induced mortality 19 (GRIM-19). GRIM-19 has been reported to interact physically with STAT3 and inhibit STAT3-dependent signal transduction. We used the nona-arginine (R9)-protein transduction domain (R9-PTD) as a protein carrier to induce high levels of GRIM-19 expression in vitro and in vivo. We generated an R9-PTD-containing GRIM-19 fusion protein (rR9-GRIM19) and successfully induced overexpression in the cytoplasm of cancer cells. Analysis of the expression of downstream molecules of STAT3 confirmed that in vitro rR9-GRIM19 treatment of constitutively activated STAT3 (STAT3c) cancer cells significantly reduced STAT3-dependent transcription. Moreover, intratumoral injections of rR9-GRIM19 in STAT3c cancer-bearing mice significantly suppressed tumor growth. These results suggest that intratumoral injections of rR9-GRIM19 have potential as a novel anticancer therapy in STAT3c cancer due to their ability to inhibit STAT3-mediated signal transduction without major systemic side effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1538-8514
pubmed:author
pubmed:copyrightInfo
(c) 2010 AACR.
pubmed:issnType
Electronic
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2333-43
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Overexpression of GRIM-19 in cancer cells suppresses STAT3-mediated signal transduction and cancer growth.
pubmed:affiliation
Department of Dermatology, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't