國家衛生研究院 NHRI:Item 3990099045/2264

NHRI > Institute of Molecular and Genomic Medicine > Chi-Ying F. Huang(1998-2005) > Periodical Articles > Item 3990099045/2264

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Title:	Induction of cyclooxygenase-2 by staurosporine through the activation of nuclear factor for IL-6 (NF-IL6) and activator protein 2 (AP2) in an osteoblast-like cell line
Authors:	Wang, CY;Lei, HJ;Huang, CYF;Zhang, ZJ;Mukherjee, AB;Yuan, CJ
Contributors:	Division of Molecular and Genomic Medicine
Abstract:	The induction of cyclooxygenase-2 (COX-2) plays a crucial role in many physiological and pathological processes. The expression of the COX-2 gene is regulated by many extracellular stimuli, including growth factors, cytokines, and tumor promoters. Staurosporine, a potential anti-tumor drug, was found recently to up-regulate the expression of the COX-2 gene in the mouse osteoblast-like cell line MC3T3-E1. The ability of staurosporine to induce the expression of the COX-2 gene was investigated using luciferase reporters controlled by various COX-2 core promoter regions. Two cis-acting sites for activator protein 2 (AP2) and nuclear factor for IL-6 (NF-IL6), respectively, were identified as responsible for the staurosporine-mediated COX-2 up-regulation. Mutational analysis further verified that both NF-IL6 and AP2 are involved in this process. Further studies showed the stimulatory effect of staurosporine on luciferase activity to be both time- and concentration-dependent. Luciferase activity could be induced at as low as 5 nM staurosporine and reached a maximum at around 20 nM. At 50 nM, the stimulatory effect of staurosporine on luciferase activity reached a maximum at about 8 hr and fell rapidly following 10 hr of incubation. Interestingly, a selective protein kinase C inhibitor, 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl) maleimide (GF109203X), failed to stimulate luciferase activity under the same conditions. This finding implies that staurosporine-mediated COX-2 gene expression is specific and independent of protein kinase C activity. (C) 2002 Elsevier Science Inc. All rights reserved.
Keywords:	Pharmacology & Pharmacy
Date:	2002-07-15
Relation:	Biochemical Pharmacology. 2002 Jul;64(2):177-184.
Link to:	http://dx.doi.org/10.1016/S0006-2952(02)01106-1
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0006-2952&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000177233400003
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0037099471
Appears in Collections:	[Chi-Ying F. Huang(1998-2005)] Periodical Articles

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