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Increase in PGE2 biosynthesis induces a Bax dependent apoptosis correlated to patients’ survival in glioblastoma multiforme

Abstract : Prostaglandin E 2 plays multiple roles both in the physiology and the physiopathology of human brain, which are not completely understood. We have identified in a subset of human glioblastoma multiforme (GBM) tumors, the most common form of adult brain cancer, an increased expression of mPGES-1, the enzyme which catalyses the isomerization of PGH 2 into PGE 2 downstream of cyclooxygenase 2 (COX-2). The sensitivity of primary cultures of GBM to apoptosis was augmented by the overexpression of mPGES-1, whereas the knockdown of its expression by shRNA decreased the apoptotic threshold in vitro and stimulated tumor growth in vivo. Adding extracellular PGE 2 in the culture medium failed to reproduce mPGES-1 effect on the cell viability in vitro. However, the intracellular injection of PGE 2 induced a dose-dependent apoptosis in GBM cultures, which was dependent on the presence of Bax, a pro-apoptotic protein. We show that PGE 2 physically associates with Bax, triggering its apoptotic-like change in conformation and its subsequent association with mitochondria. Our results raise questions about the role of PGE 2 in the control of apoptosis and in its potential impact in central nervous system pathologies.
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https://www.hal.inserm.fr/inserm-03369894
Contributor : Lisenn Lalier Connect in order to contact the contributor
Submitted on : Thursday, October 7, 2021 - 4:15:24 PM
Last modification on : Saturday, October 9, 2021 - 3:38:15 AM

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Lisenn Lalier, P-F Cartron, F Pedelaborde, C Olivier, D Loussouarn, et al.. Increase in PGE2 biosynthesis induces a Bax dependent apoptosis correlated to patients’ survival in glioblastoma multiforme. Oncogene, Nature Publishing Group, 2007, 26, pp.4999 - 5009. ⟨10.1038/sj.onc.1210303⟩. ⟨inserm-03369894⟩

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