We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Nitric oxide upregulates the cyclooxygenase-2 expression through the cAMP-response element in its promoter in several cancer cell lines.
- Authors
Seok-Woo Park; Myung-Whun Sung; Dae-Seog Heo; Hiroyasu Inoue; Seon-Hui Shim; Kwang-Hyun Kim
- Abstract
We previously showed that nitric oxide (NO) induces overexpression of cyclooxygenase-2 (COX-2) and production of prostaglandin E2 in cancer cells. Here, we investigated the mechanisms by which NO induces COX-2 expression in cancer cells. We found that the cAMP-response element (CRE) is a critical factor in NO- induced COX-2 expression in all cells tested. We found that in cancer cells, three transcription factors (TFs) - cAMP response element-binding protein (CREB), activating transcription factor-2 (ATF-2) and c-jun, bound the CRE in the COX-2 promoter, and their activities were increased by addition of the NO donor, S-nitroso-N- acetyl-D ,L-penicillamine (SNAP). NO-induced activation of soluble guanylate cyclase (sGC), p38 and c-Jun NH2- terminal kinase (JNK) upregulated the three TFs, leading to COX-2 overexpression. Addition of dibutyryl-cGMP (db-cGMP) induced COX-2 expression in a manner similar to SNAP; this induction was blocked by a p38 inhibitor (SB202190), but not by a JNK inhibitor (SP600125). NO-induced cGMP was found to activate CREB and ATF-2 in a p38, but not c-jun-dependent manner, while NO induced JNK in a cGMP-independent manner, leading to subsequent activation of c-jun and ATF-2. These results suggest that the low concentrations of endogenous NO present in cancer cell may induce the expression of many genes, including COX-2, which promotes the growth and survival of tumor cells.
- Subjects
CYCLOOXYGENASE 2; CELL lines; CYCLOOXYGENASES; CELLULAR pathology; TRANSCRIPTION factors; ANTIARTHRITIC agents
- Publication
Oncogene, 2005, Vol 24, Issue 44, p6689
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1208816