Document Detail


Absence of STAT1 disturbs the anticancer effect induced by STAT3 inhibition in head and neck carcinoma cell lines.
MedLine Citation:
PMID:  19424608     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The family of signal transducers and activators of transcription (STAT) are transcription factors. Among them, STAT1 is associated with an apoptosis pathway, while STAT3 is associated with tumorigenicity in various cancer cells. In order to investigate the primary roles of STAT1 and STAT3 in head and neck squamous cell carcinoma (HNSCC), we blocked STAT3 with two JAK inhibitors: AG490 (JAK2-STAT3 pathway inhibitor) and JAK total inhibitor. When we inhibited STAT3 with AG490, significant cell death was observed. However, in the case of JAK kinase total inhibitor, no cell growth retardation was observed. We focused on the role of STAT1 in this phenomenon. Suppression of STAT1 by si-RNA resulted in increased cell survival. Furthermore, the growth inhibitory effect of AG490 was reduced by treatment with si-RNA of STAT1. These results reveal that STAT1 is required to promote the tumor killing effect of STAT3 inhibition in HNSCC.
Authors:
Seon-Hui Shim; Myung-Whun Sung; Seok-Woo Park; Dae Seog Heo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of molecular medicine     Volume:  23     ISSN:  1107-3756     ISO Abbreviation:  Int. J. Mol. Med.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-08     Completed Date:  2009-07-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9810955     Medline TA:  Int J Mol Med     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  805-10     Citation Subset:  IM    
Affiliation:
Department of Molecular Tumor Biology, College of Medicine, Seoul National University, Seoul, Korea.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Blotting, Western
Carcinoma, Squamous Cell / drug therapy
Cell Death / drug effects*
Cell Line, Tumor
Head and Neck Neoplasms / drug therapy
Humans
RNA, Small Interfering
STAT1 Transcription Factor / genetics,  metabolism,  physiology*
STAT3 Transcription Factor / antagonists & inhibitors*,  metabolism
Tyrphostins / pharmacology*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/RNA, Small Interfering; 0/STAT1 Transcription Factor; 0/STAT1 protein, human; 0/STAT3 Transcription Factor; 0/Tyrphostins; 0/alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide

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