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Title: The role of prokineticin 1 in endometrial function
Author: Evans, Jemma
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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Investigation of the temporal pattern of expression of PROK1 and PROKR1 in pregnant and non-pregnant endometrium has shown (a) both factors to be expressed in the normal cycling endometrium with an elevation in PROK1 expression during the secretory phase of the cycle and (b) further elevation of both factors in the pregnant decidua when compared with the non-pregnant endometrium. Expression of PROK1 was down-regulated in endometrial cancer tissue compared with secretory phase endometrium, suggesting PROK1-PROKR1 is not involved in the pathogenesis of this disease. PROK1 and PROKR1 localise to the glandular epithelium, stroma and vasculature of the non-pregnant and pregnant endometrium. Additionally, PROK1 expression was localised in macrophages and uterine natural killer cells within the stromal compartment. In order to investigate signalling and the role of PROK1 in endometrial epithelial cells, an endometrial epithelial cell line (Ishikawa cells) stably expressing PROKR1 was utilised. PROK1-PROKR1 interaction, using this cell line, induced a signalling cascade involving phosphorylation of cSrc, epidermal growth factor receptor (EGFR) and ERK ½. This cascade to ERK ½ phosphorylation was dependent on activation of G1 protein, PLC-β and Ca2+ as well as phosphorylation of sSrc and EGFR and activation of the small GTPase Ras. Gene array analysis was subsequently conducted using RNA extracted from PROKR1 Ishakawa cells treated with vehicle or 40nM PROK1 for 8 hours. A total of 277 genes were differentially expressed in response to PROK1 (226 genes were up-regulated and 51 genes down-regulated). A number of these genes have suggested roles in implantation. These include: cyclooxygenase-2 (COX-2), leukaemia inhibitor factor (LIF), Interleukin (IL)-6, IL-11 and Heparin bound-EGF. Finally, the expression of PROK1 and LIF in the human endometrium can be mediated by embryonic hCG secretion. Treatment of PROKR1 Ishikawa cells and first trimester deciduas with 1 1U hCG results in sequential increase in PROK1 and LIF expression.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available