標題: 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
作者: Wang, CY
Lei, HJ
Huang, CYF
Zhang, ZJ
Mukherjee, AB
Yuan, CJ
生物科技學系
Department of Biological Science and Technology
關鍵字: staurosporine;NF-IL6;AP2;cyclooxygenase-2
公開日期: 15-七月-2002
摘要: 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.
URI: http://dx.doi.org/10.1016/S0006-2952(02)01106-1
http://hdl.handle.net/11536/28662
ISSN: 0006-2952
DOI: 10.1016/S0006-2952(02)01106-1
期刊: BIOCHEMICAL PHARMACOLOGY
Volume: 64
Issue: 2
起始頁: 177
結束頁: 184
顯示於類別:期刊論文


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  1. 000177233400003.pdf