Studies on the Function of Selenium Binding Protein 1 and its Relevance to Prostate Cancer Outcome
thesisposted on 28.10.2014, 00:00 by Emmanuel Ansong
SBP1 levels are reported to be consistently lower in human tumors compared to normal tissue, and low tumor SBP1 levels are predictive of poor outcome of several cancer types, although its ability to predict prostate cancer outcome has never been examined. Therefore, it is hypothesized that low SBP1 is able to predict recurrence of prostate cancer and it may be useful in determining which patients will recur after radical prostatectomy. In order to examine if SBP1 levels are predictive of prostate cancer recurrence, tissue from post-radical prostatectomy prostate cancer patients who experienced biochemical recurrence were compared to non-recurred controls. Patients in the lowest quartile of SBP1 expression were significantly more likely to recur compared with patients with higher expression, extending the association of low SBP1 and poor cancer prognosis to include prostate cancer. In order to gain a better understanding of the function of SBP1, and why its low levels are associated with poor outcome, the response of cells with and without SBP1 to the DNA damaging agent 5-FUra was examined. Following of 5-FUra treatment, cells expressing SBP1 proliferated significantly less than SBP1 null cells.Additionally, SBP1 expression was led to phosphorylation of serine-15 on p53, a post translational modification which facilitates p53 cell cycle arrest/apoptotic pathway. Taken together, the data collected from this study indicates that SBP1 affects the consequences of DNA damage in the cell, which may be the reason why its low levels lead to poor prognosis in cancer patients.