Abstract | BACKGROUND:
Prostaglandin E(2) ( PGE(2)) has been shown to modulate angiogenesis and tumour progression via the E-series prostanoid-2 (EP2) receptor. Endometrial adenocarcinomas may be exposed to endogenous PGE(2) and exogenous PGE(2), present at high concentration in seminal plasma. METHODS: RESULTS: Seminal plasma and PGE(2) induced a significant up-regulation of FGF2 expression in EP2 sense but not parental untransfected Ishikawa (wild-type) cells (P < 0.05). These effects were inhibited by co-treatment with EP2 receptor antagonist or inhibitors of protein kinase A, c-Src, epidermal growth factor receptor (EGFR) kinase or extracellular signal-regulated kinase (ERK) signalling. The treatment of EP2 sense cells with seminal plasma induced cAMP accumulation and phosphorylation of c-Src, EGFR kinase and ERK via the EP2 receptor. Finally, seminal plasma and PGE(2) significantly increased FGF2 mRNA expression in endometrial adenocarcinoma tissue explants via the EP2 receptor (P < 0.05). CONCLUSIONS: Seminal plasma and PGE(2) can similarly activate FGF2 expression and EP2 receptor signalling in endometrial adenocarcinoma cells. These data highlight the potential for seminal plasma exposure to facilitate tumorigenesis-angiogenesis in endometrial adenocarcinomas in vivo.
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Authors | S Battersby, K J Sales, A R Williams, R A Anderson, S Gardner, H N Jabbour |
Journal | Human reproduction (Oxford, England)
(Hum Reprod)
Vol. 22
Issue 1
Pg. 36-44
(Jan 2007)
ISSN: 0268-1161 [Print] England |
PMID | 16905765
(Publication Type: Journal Article)
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Chemical References |
- PTGER2 protein, human
- Receptors, Prostaglandin E
- Receptors, Prostaglandin E, EP2 Subtype
- Fibroblast Growth Factor 2
- Cyclic AMP
- ErbB Receptors
- Proto-Oncogene Proteins pp60(c-src)
- Extracellular Signal-Regulated MAP Kinases
- Dinoprostone
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Topics |
- Adenocarcinoma
(metabolism)
- Cell Line, Tumor
- Cyclic AMP
(metabolism)
- Dinoprostone
(physiology)
- Endometrial Neoplasms
(metabolism)
- ErbB Receptors
(physiology)
- Extracellular Signal-Regulated MAP Kinases
(physiology)
- Female
- Fibroblast Growth Factor 2
(biosynthesis)
- Gene Expression Regulation
- Humans
- Male
- Microscopy, Confocal
- Microscopy, Fluorescence
- Phosphorylation
(drug effects)
- Proto-Oncogene Proteins pp60(c-src)
(metabolism)
- Receptors, Prostaglandin E
(physiology)
- Receptors, Prostaglandin E, EP2 Subtype
- Semen
(physiology)
- Signal Transduction
- Transcriptional Activation
(physiology)
- Up-Regulation
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