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Title: The Role of Adipokines in Prostate Cancer
Author: Mistry, Tina
ISNI:       0000 0001 3411 2084
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2007
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The aim of this study was to investigate the role of the adipokines adiponectin and visfatin as molecular mediators between obesity and prostate cancer. Adiponectin (decreased with obesity) has been proposed as an anti-cancer adipokine. Adiponectin receptors (Adipo-Rl, Adipo-R2) were detected in LNCaP and PC3 prostate cancer cell lines and benign and malignant prostate tissue using RT-PCR, western blotting and immunochemical techniques, and their expression was found to be differentially regulated by a variety of hormones/cytokines that play key roles in the pathophysiology of obesity and/or prostate cancer. Preliminary studies presented here suggest functionality of these receptors was demonstrated by their ability to modulate 5'AMP- activated protein kinase, p44/42 and p38 mitogen-activated protein kinase activity in response to treatment with either full-length (fAd) and/or globular (gAd) adiponectin, although further studies are required to confirm this. PC3 cell proliferation was significantly inhibited and stimulated by high concentrations of fAd and gAd, respectively; when combined with high concentrations of leptin, both fAd and gAd significantly inhibited PC3 proliferation. Furthermore, the changes in proliferation following treatment with fAd/gAd ± leptin were associated with corresponding changes in p53 and PTEN tumour suppressor gene and bcl-2 and c-myc oncogene expression, suggesting that the anti-proliferative effects of adiponectin may partly be via modulation ofthese genes. The novel adipokine visfatin, directly correlated with obesity, has also been identified as NMPRTase, a key enzyme involved in NAD synthesis. This study demonstrates the novel expression of intracellular visfatin in LNCaP and PC3· cells and benign and malignant prostate tissue, and its regulation by androgens, IL-6 and IGF-L Additionally, the preliminary data presented here indicate a proliferative role for exogenous visfatin, particularly in the presence ofIGF-l. The data presented here indicate potential roles for adiponectin and visfatin in prostate carcinogenesis. This study provides a foundation upon which further studies may be performed that could allow novel therapeutic agents to be developed in the future.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available