Modulation of growth control mechanisms in prostate cancer cells by fatty acids
Hypothesis: The n-6 fatty acids could possibly stimulate the growth of prostate cancer cells through activation of the DAG and PKC pathway and the n-3 fatty acids could possibly inhibit cell growth through the induction of the apoptotic pathway controlled by the ceramides, p53 and Bcl2. However, up or down regulation of either of these pathways could coexist in the stimulatory and inhibitory mechanisms of different fatty acids on the growth of prostate cancer cells. This research project is designed to test the first half of the hypothesis on stimulation of cell growth mediated by activation of the PKC pathway. Objectives: 1. To critically analyse the effect of a wide range of concentrations of different fatty acids on the proliferation of human prostatic cells (normal & malignant), in vitro. 2. To identify if fatty acids have an influence on the expression of a well established tumour marker in prostate cancer, prostate specific antigen (PSA), in vitro. 3. To analyse if changes in PSA expression correlate with the changes in cell proliferation induced by fatty acids and thereby to confirm if PSA expression could be a valuable intermediate bio-marker in studying the mechanistic effects of fatty acids on prostate cancer cells. 4. To analyse the effect of different fatty acids on the total protein kinase: C activity in prostate cancer cells, in vitro. 5. To identify which of the eleven known isoforms of PKC could be modulated by fatty acids. The Future: Studies in the immediate future will need to analyse the effects of different fatty acids on apoptosis in prostatic cell lines. Studies should also analyse the effects of different fatty acids on the expression of oncogenes such as p53 and Bcl2 in prostate cancer cells. Further studies to evaluate the effect of fatty acids on the regulation of growth factors and transcription factors will add more structure to this research.