COX-1 is coupled with mPGES-1 and ABCC4 in human cervix cancer cells.
Cyclooxygenases are key enzymes in the arachidonic acid metabolism. Their unstable intermediate, prostaglandin H(2), is further metabolized to bioactive lipids by various downstream enzymes. In this study, utilizing short hairpin RNAs, we prepared a cell line of human cervix carcinoma with stable down-regulated cyclooxygenase-1 (COX-1) to assess the impact of COX-1 reduction on the downstream enzymes. We found a significant microsomal prostaglandin E synthase-1 (mPGES-1) suppression. In addition, mRNA expression of multidrug resistance protein 4 (MRP4, ABCC4), supposed to take part in antiviral and anticancer drug transport from cells, was up-regulated after COX-1 down-regulation. Our findings indicate that mPGES-1, believed to be coexpressed preferentially with cyclooxygenase-2, may be coupled to COX-1. ABCC4 up-regulation further supports the assumption of its involvement in prostanoid transport.
Radilova
Hana
H
GENERI BIOTECH s.r.o, Hradec Kralove, Czech Republic. hana.radilova@generi-biotech.com
Libra
Antonin
A
Holasova
Sarka
S
Safarova
Martina
M
Viskova
Alena
A
Kunc
Filip
F
Buncek
Martin
M
D001692:Biological Transport; D045744:Cell Line, Tumor; D051545:Cyclooxygenase 1 / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D020868:Gene Silencing; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D000071876:Prostaglandin-E Synthases; D011453:Prostaglandins / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000473:pathology
D051545:Cyclooxygenase 1; D019746:Intramolecular Oxidoreductases; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000071876:Prostaglandin-E Synthases; D011453:Prostaglandins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C073492:ABCC4 protein, human; C000605862:PTGES protein, human