Seminal plasma activates cyclooxygenase-2 and prostaglandin E2 receptor expression and signalling in cervical adenocarcinoma cells.
Enhanced cyclooxygenase (COX) expression and prostaglandin E2 (PGE2) synthesis are regarded as promoters of neoplastic cell proliferation and angiogenesis. Expression of COX-2 and synthesis of PGE2 are up-regulated in cervical carcinomas. In sexually active women, growth and invasiveness of neoplastic cervical epithelial cells may be also under the direct influence of PGE2 present in seminal plasma. The aims of this study were to investigate the effect of seminal plasma and PGE2 on the expression of COX-2 and expression and signalling of the PGE2 receptor subtypes (EP1-EP4) in HeLa (cervical adenocarcinoma) cells. Treatment of HeLa cells with seminal plasma or PGE2 resulted in up-regulation of COX-2 expression (P < 0.05). In addition, seminal plasma induced the mRNA expression of EP1, EP2 and EP4 receptors, whilst PGE2 treatment of HeLa cells induced the expression of the EP4 receptor (P < 0.05). This was coincident with a rapid accumulation of adenosine 3',5'-cyclic monophosphate (cAMP) in HeLa cells stimulated with seminal plasma or PGE2, which was greater in seminal plasma stimulated cells compared with PGE2 stimulated cells (P < 0.05). Subsequently, we investigated whether the effect of seminal plasma on cAMP signalling in HeLa cells was mediated via the cAMP-linked EP2/EP4 receptors. Stimulation of HeLa cells with seminal plasma or PGE2 resulted in an augmented cAMP accumulation in cells transfected with the EP2 or EP4 receptor cDNA compared with control transfected cells (P < 0.05). These data suggest that, in sexually active women, seminal plasma may play a role in modulating neoplastic cell function and cervical tumorigenesis.
Sales
Kurt J
KJ
MRC Human Reproductive Sciences Unit, Academic Centre, 49 Little France Crescent, Old Dalkeith Road, Edinburgh EH16 4SB, UK.
Katz
Arieh A
AA
Millar
Robert P
RP
Jabbour
Henry N
HN
D000230:Adenocarcinoma / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics*; D011982:Receptors, Prostaglandin / Q000096:biosynthesis / Q000235:genetics*; D012661:Semen / Q000378:metabolism*; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
D007527:Isoenzymes; D008565:Membrane Proteins; D011982:Receptors, Prostaglandin; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone