Studies on the Function of Selenium Binding Protein 1 and its Relevance to Prostate Cancer Outcome

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

Additional file 1: of A comparison of intrathecal magnesium and ketamine in attenuating remifentanil-induced hyperalgesia in rats

Supplementary material. (XLSX 13 kb

Quantitative identification and bioinformatics analysis of tumor tissue proteins assayed by iTRAQ.

<p><b>(A)</b> All 132 differentially accumulated proteins were classified into three groups: biological process, molecular function, and cellular component through GO analysis. <b>(B)</b> The numbers of lipid/glucose metabolism-related proteins were shown through GO analysis.</p

Identified differentially accumulated proteins related to glucose metabolism.

<p>Identified differentially accumulated proteins related to glucose metabolism.</p

Tumor inhibition of SBP1 was associated with multiple signaling pathways <i>in vivo</i>.

<p>Several typical markers of different signaling pathways were examined using iTRAQ proteomic analysis protein samples. These cancer related signaling pathways respond differently to SBP1 induction.</p

Hypothetic pathways of SBP1-mediated anti-cancer functions <i>in vivo</i>.

<p>SBP1-mediated anti-cancer effects may be through lipid/glucose metabolism. The possible functional regulation between SBP1 and related proteins is illustrated.</p

Quantitative identification and bioinformatics analysis of tumor tissue proteins assayed by iTRAQ.

<p><b>(A)</b> All 132 differentially accumulated proteins were classified into three groups: biological process, molecular function, and cellular component through GO analysis. <b>(B)</b> The numbers of lipid/glucose metabolism-related proteins were shown through GO analysis.</p

Identified differentially accumulated proteins related to lipid metabolism.

<p>Identified differentially accumulated proteins related to lipid metabolism.</p

SBP1 induction in nude mice inhibited tumor growth of xenografts.

<p><b>(A)</b> SBP1 induced by doxycycline in HCT116-TetSBP1 cells were validated by immunoblot analysis. <b>(B)</b> Photographs illustrate representative tumors in xenografts with SBP1 induction (TetSBP1, right) compared to tumors without SBP1 induction (Act, left). 10 mice in total. <b>(C-D)</b> SBP1 induction results in a decline of tumor volume and weight. Results were analyzed with Student’s t-test and shown as mean±SD. **P<0.01.</p

SBP1 induction suppressed tumor metastasis <i>in vivo</i>

<p><b>(A)</b> Representative images of lungs and hematoxylin and eosin (HE)-staining of lungs isolated from mice that received tail vein injection of HCT116-Act cells (Act) and HCT116-TetSBP1 cells (TetSBP1). Each group contains 5 mice. Arrows illustrates the visible nodules and metastatic nodules in lung. Scale bar = 200 μm. <b>(B)</b> SBP1 induction inhibits tumor metastasis <i>in vivo</i>. The numbers of pulmonary metastatic nodules were counted under microscope and analyzed with Student’s t-test. Results are shown as mean±SD. **P<0.01.</p