PMID- 12123737
OWN - NLM
STAT- MEDLINE
DCOM- 20020816
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 64
IP  - 2
DP  - 2002 Jul 15
TI  - 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.
PG  - 177-84
AB  - 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.
FAU - Wang, Chiu-Ya
AU  - Wang CY
AD  - Department of Biological Science and Technology, National Chiao Tung University, 
      75 Po-Ai Street, Hsinchu 30050, Taiwan, ROC.
FAU - Lei, Huey-Jing
AU  - Lei HJ
FAU - Huang, Chi-Ying Fred
AU  - Huang CY
FAU - Zhang, Zhongjian
AU  - Zhang Z
FAU - Mukherjee, Anil B
AU  - Mukherjee AB
FAU - Yuan, Chiun-Jye
AU  - Yuan CJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indoles)
RN  - 0 (Isoenzymes)
RN  - 0 (Maleimides)
RN  - 0 (Transcription Factor AP-2)
RN  - 0 (Transcription Factors)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - H88EPA0A3N (Staurosporine)
RN  - L79H6N0V6C (bisindolylmaleimide I)
SB  - IM
MH  - Animals
MH  - CCAAT-Enhancer-Binding Protein-beta/*metabolism
MH  - Cell Line
MH  - Cyclooxygenase 2
MH  - DNA-Binding Proteins/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Induction/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Genes, Reporter
MH  - Indoles/pharmacology
MH  - Isoenzymes/*biosynthesis/genetics
MH  - Luciferases/metabolism
MH  - Maleimides/pharmacology
MH  - Mice
MH  - Mutation
MH  - Osteoblasts/drug effects/enzymology/metabolism
MH  - Promoter Regions, Genetic/*drug effects/genetics
MH  - Prostaglandin-Endoperoxide Synthases/*biosynthesis/genetics
MH  - Staurosporine/*pharmacology
MH  - Time Factors
MH  - Transcription Factor AP-2
MH  - Transcription Factors/*metabolism
MH  - Up-Regulation
EDAT- 2002/07/19 10:00
MHDA- 2002/08/17 10:01
CRDT- 2002/07/19 10:00
PHST- 2002/07/19 10:00 [pubmed]
PHST- 2002/08/17 10:01 [medline]
PHST- 2002/07/19 10:00 [entrez]
AID - S0006295202011061 [pii]
AID - 10.1016/s0006-2952(02)01106-1 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2002 Jul 15;64(2):177-84. doi: 10.1016/s0006-2952(02)01106-1.