No description available.

No description available.

No description available.

No description available.

Cancer cells have the ability to survive when oxygen is limiting, and upregulate the pathway of fatty acid synthesis, owing in part to alterations in their metabolism. I compared the metabolic phenotypes of the prostate cancer cell lines LNCaP, DU145, and PC3 assessing energy metabolism, and metabolic gene expression. I also explored the plasticity of the metabolic phenotype following passage, selection and in vivo growth. Finally, I explored the sensitivity of the fatty acid synthesis pathway to low oxygen. LNCaP cells had a more oxidative phenotype based on oxygen consumption, lactate production, enzyme assays, and mRNA levels. While DU145 and PC3 cells were more glycolytic, they were unresponsive to dichloroacetate (DCA), and dinitrophenol (DNP), stimulators of oxygen consumption. Mitochondrial dysfunction in the PC3 and DU145 cells may explain this phenomenon, for they possessed normal cardiolipin levels but lower mitochondrial enzyme activities (cytochrome oxidase (COX), citrate synthase (CS)). When LNCaP cells were subjected to high passage, with and without clonal selection, the derived lines acquired a dysfunctional oxidative phenotype, becoming more glycolytic. Clonal selection appeared to have the most dramatic effect on cellular metabolism. This finding is supported by decreased oxygen consumption, increased lactate production, and a reduction in the activity of the oxidative enzymes CS and COX in the clonally selected LNCaP-luc cell line. Similar to the DU145 and PC3 cells, NAO fluorescence indicates that the oxidative impairment in these LNCaP-derived lines may be due to a reduction in mitochondrial activity. The pattern of metabolic gene expression iii seen in vitro was unaffected when LNCaP cells were grown as subcaspular and muscle xenografts in immunodeficient mice, though xenografts did exhibit indications of an hypoxic response (elevated VEGF mRNA). Oxygen deprivation in vitro increased mRNA for HIF and responsive genes but not SREBP responsive genes. Similarly, oxygen deprivation had no influence on triglyceride levels in any of the lines suggesting that the SREBP axis may not be directly modulated by oxygen levels. Collectively these studies demonstrate differences in the metabolism of these prostate cancer models, with important ramifications of therapeutic strategies involving metabolic targets. / Thesis (Master, Biology) -- Queen's University, 2008-09-25 17:28:13.418

No description available.

Prostate cancer, one of the most common cancers among men, can be relatively harmless or extremely aggressive. The most widely used biomarker for the disease, the PSA test, is not independently diagnostic or prognostic of prostate cancer. One of the main challenges of prostate cancer research is to find reliable and effective prognostic biomarkers that will predict cancer recurrence following surgery, in order to identify clinically significant prostate cancer and improve management of the disease. In recent years, microRNAs (miRNAs) have been identified as master regulators of cellular processes, and dysregulated miRNAs have been associated with cancer development and progression. The intent of my PhD research program was to uncover novel miRNAs that contribute to prostate cancer pathogenesis in order to assess their potential as predictors of clinical progression. By analyzing a large cohort of primary prostate cancer samples, we have discovered that microRNA-221 (miR-221) is associated with metastasis and biochemical recurrence in prostate cancer, and is downregulated in TMPRSS2:ERG fusion gene- positive tumors. In addition, we have determined that microRNA-182 (miR-182) is overexpressed in prostate cancer and is associated with increased metastasis and clinical progression by targeting a tumors suppressor Forkhead box O1 (FOXO1). Overall, this work introduces novel candidate miRNA genes and downstream targets that are aberrantly expressed in more aggressive prostate cancer, and presents a potentially significant role for miRNAs as prognostic biomarkers that are associated with clinical progression, and perhaps aids in defining how miRNAs might one day serve as anti-cancer therapeutic agents.

Estrogens maintain the appropriate androgen-estrogen balance for normal regulation of the structure and function of the male reproductive tract, including the prostate gland. This research investigated viability of cells and expression of selected genes in prostate carcinoma cells (PC-3) exposed to bisphenol A (BPA), an estrogen-like substance present in a number of plastic materials. PC-3 cells are able to metabolize BPA at concentrations below 100 µM. BPA exposure at concentrations between 1nM and 100 µM does not increase or significantly reduce cell viability of these cells. Although the genes investigated in this study (GSTP1 and MGMT) did not show a significant change in expression following in vitro exposure to BPA, the positive control ethinyl estradiol (EE2) caused an increase in GSTP1 expression at mRNA level. These results indicate that BPA does not affect the viability of prostate cells, and motivate a need for further research to identify other genes that could be affected by BPA.

Thesis (Ph. D.)--University of Hawaii at Manoa, 1996. / Includes bibliographical references (leaves 129-135). / Microfiche. / xv, 135 leaves, bound ill. 29 cm

Thesis (M. Phil.)--University of Hong Kong, 1996. / Includes bibliographical references (leaf 135-164).