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Title: The role of QRFP & GPR103 in human prostate cancer
Author: Kawan, Mohamed
ISNI:       0000 0004 6350 7335
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2016
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Prostate cancer is the leading cause of non-cutaneous malignancy and is the second most commonly diagnosed cancer among men after lung cancer. QRFP is a secreted protein that is extensively expressed in the brain with highest expression levels in the medulla, pituitary gland, cerebellum, retina, and vestibular nucleus; in the periphery it is expressed in the adipose tissue prostate gland, bladder, colon, testis and in the parathyroid and thyroid gland. QRFP is a member of the RF amide neuropeptide family. This family might be implicated in extensive array of biological activities for instance, food intake, cardiovascular functioning, blood pressure, analgesia, aldosterone secretion and locomotor activity, resulting in orexinergic activities. It is suggested that obesity is one of the contributing factors for aggressive form of prostate cancer. There is a strong association between adipokines and aggressive form of various cancers. QRFP has been recently described as an adipokine that exerts its functions via activation of the G protein coupled receptor GPR103. At present the role of the QRFP and GPR103 in prostate cancer has not been explored in detail. I studied the potential role of the adipokine QRFP in prostate cancer. The three prostate cancer cell lines: PC3, DU145 (Orbetzova, 2012) and LNCaP (androgen-sensitive) were used as models for my studies. Nevertheless, no studies to date have investigated the effects of QRFP and GPR103 in prostate cancer. This prompted me to examine the expression and function of QRFP and GPR103 in the human prostate cells. Also I sought to identify the role of QRFP and GPR103 in prostate cancer. The novel data presented in this study demonstrates that QRFP & GPR103 genes and protein are expressed in both human prostate tissue and prostate cancer cell lines. Expression of both QRFP and GPR103 were higher in PCa tissues compared to controls. Moreover, an ELISA detected circulate QRFP serum levels were lower in human cancer patients compared to benign and healthy group. Stimulation with QRFP induced MAPK signalling cascades, AKT, AGR-2 expression, MMP 2, Caspase-3 and AMPK in PC3 & DU145 cells. QRFP also increased PC3 & DU145 cells migration and invasion, nonetheless QRFP showed induced suppression cell proliferation in PC3, DU145 and LNCaP cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RC Internal medicine