Loss of prostaglandin D2 synthase: a key molecular event in the transition of a low-grade astrocytoma to an anaplastic astrocytoma.
Reduction in the mRNA and protein expression of lipocalin-like prostaglandin D(2) (PGD(2)) synthase (PGDS), the main arachidonic acid metabolite produced in neurons and glial cells of the central nervous system, is a significant biological event involved in the malignant progression of astrocytomas and is predictive of poor survival. In vitro, the addition of the main PGDS metabolite, PGD(2), to A172 glioblastoma cells devoid of PGDS resulted in antiproliferative activity and cell death. In vitro PGD(2) substitution also enhanced the efficacy of cyclo-oxygenase-2 inhibitors. This finding has exciting implications for early interventional efforts for the grade 2 and 3 astrocytomas.
Hormones and Cancer Group, Cancer Genetics Laboratory, Kolling Institute of Medical Research, Reserve Road, St. Leonards, New South Wales, 2065 Australia.
Cathy A
CA
Payne
Sanaz
S
Maleki
Marinella
M
Messina
Maree G
MG
O'Sullivan
Glenn
G
Stone
Nathan R
NR
Hall
Jonathon F
JF
Parkinson
Helen R
HR
Wheeler
Raymond J
RJ
Cook
Michael T
MT
Biggs
Nicholas S
NS
Little
Charles
C
Teo
Bruce G
BG
Robinson
Kerrie L
KL
McDonald
D001254:Astrocytoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D019175:DNA Methylation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases / Q000172:deficiency* / Q000235:genetics; D007438:Introns / Q000235:genetics; D054834:Lipocalins / Q000235:genetics; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D015230:Prostaglandin D2 / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D016019:Survival Analysis
D016861:Cyclooxygenase Inhibitors; D054834:Lipocalins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2