Obesity is a major health problem worldwide and its effects on the cardiovascular system are well documented. It also leads to the development of metabolic disease such as insulin resistance and diabetes. There is evidence that obesity leads to an increased risk of developing numerous malignancies. Indeed, obese individuals diagnosed with malignancy tend to have poorer outcomes in terms of survival. A possible explanation for this is through the action of obesity-related cytokines (adipokines). These may play a role in either propagating, or perpetuating carcinogenesis and I explored the role of one particular adipokine: chemerin in prostate cancer. Prostate cancer cell lines (PC3 & LNCaP) were used for cell proliferation, migration, invasion and apoptosis assays. Western blot analysis and qRT-PCR techniques were used to evaluate the effects of chemerin on levels of key intracellular agents of carcinogenesis (bcl-2, p53, ERK and AKT) as well as novel, pro-cancerous genes such as anterior gradient 2 (AGR2). Serum samples were obtained from adult men with prostate disease to evaluate whether chemerin is associated with body parameters. Chemerin exerts positive effects on cellular proliferation and migration as well as inhibition of apoptosis in prostate cancer cells. These effects may be mediated by increased expression of the oncogene: bcl-2. Bcl2 expression was elevated in both cell lines after 24 hours stimulation with chemerin at increasing doses. Chemerin also appeared to cause activation of ERK and AKT pathways in prostate cancer cells as well as increased expression of the pro metastatic AGR2 gene at both the mRNA and protein level. An ELISA demonstrated chemerin behaving as an adipokine in adult men with prostate disease in keeping with previously published data. Chemerin certainly appears to play a role in prostate carcinogenesis, at least at the cellular level.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:632870 |
| Date | January 2014 |
| Creators | Williams, Kevin George |
| Publisher | University of Warwick |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://wrap.warwick.ac.uk/63889/ |
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