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http://dx.doi.org/10.5483/BMBRep.2015.48.2.081

Autocrine prostaglandin E2 signaling promotes promonocytic leukemia cell survival via COX-2 expression and MAPK pathway  

Shehzad, Adeeb (School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University)
Lee, Jaetae (Department of Nuclear Medicine, Kyungpook National University Hospital)
Lee, Young Sup (School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University)
Publication Information
BMB Reports / v.48, no.2, 2015 , pp. 109-114 More about this Journal
Abstract
The COX-2/$PGE_2$ pathway has been implicated in the occurrence and progression of cancer. The underlying mechanisms facilitating the production of COX-2 and its mediator, $PGE_2$, in cancer survival remain unknown. Herein, we investigated $PGE_2$-induced COX-2 expression and signaling in HL-60 cells following menadione treatment. Treatment with $PGE_2$ activated anti-apoptotic proteins such as Bcl-2 and Bcl-xL while reducing pro-apoptotic proteins, thereby enhancing cell survival. $PGE_2$ not only induced COX-2 expression, but also prevented casapse-3, PARP, and lamin B cleavage. Silencing and inhibition of COX-2 with siRNA transfection or treatment with indomethacin led to a pronounced reduction of the extracellular levels of $PGE_2$, and restored the menadione- induced cell death. In addition, pretreatment of cells with the MEK inhibitor PD98059 and the PKA inhibitor H89 abrogated the $PGE_2$-induced expression of COX-2, suggesting involvement of the MAPK and PKA pathways. These results demonstrate that $PGE_2$ signaling acts in an autocrine manner, and specific inhibition of $PGE_2$ will provide a novel approach for the treatment of leukemia.
Keywords
Apoptosis; Autocrine signaling; Cyclooxygenase-2; Leukemia; Prostaglandine $E_2$;
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