| First Author | Timoshenko AV | Year | 2004 |
| Journal | Int J Cancer | Volume | 108 |
| Issue | 3 | Pages | 384-9 |
| PubMed ID | 14648704 | Mgi Jnum | J:88005 |
| Mgi Id | MGI:3028814 | Doi | 10.1002/ijc.11575 |
| Citation | Timoshenko AV, et al. (2004) PGE2-mediated upregulation of iNOS in murine breast cancer cells through the activation of EP4 receptors. Int J Cancer 108(3):384-9 |
| abstractText | We report here that endogenous prostaglandin E(2) (PGE(2)) resulting from cyclooxygenase (COX)-2 expression in a highly metastatic murine breast cancer cell line C3L5 upregulates IFN-gamma + LPS-induced nitric oxide (NO) synthase (iNOS) expression and NO production. This action of PGE(2) is mediated through the EP(4) receptor in a cAMP-dependent manner. Both nonselective and selective COX-2 inhibitors suppressed IFN-gamma + LPS-induced NO production, which was largely restored by exogenous PGE(2) or EP(4) receptor agonist PGE(1) alcohol. EP(4) antagonist AH-23848B inhibited NO production with a concomitant downregulation of iNOS mRNA in IFN-gamma + LPS-stimulated cells. cAMP dependence of NO production by cells under inducible conditions was demonstrated by the use of known modulators of intracellular cAMP. Since both COX-2 and iNOS are implicated in breast cancer progression, our findings of EP(4) receptor-mediated upregulation of iNOS in COX-2-expressing breast cancer cells suggest that blocking COX-2 and/or EP(4) may provide a simple therapeutic modality in this tumor model. |
