Journal
ONCOGENE
Volume 26, Issue 34, Pages 4999-5009Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1210303
Keywords
gliomas; cyclooxygenase; prostaglandin synthase; apoptosis; Bax; PGE(2)
Ask authors/readers for more resources
Prostaglandin E-2 plays multiple roles both in the physiology and the physiopathology of human brain, which are not completely understood. We have identi. ed 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 PGE2 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available