Submitted to: The Prostate Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/29/2011
Publication Date: 6/15/2012
Publication URL: http://handle.nal.usda.gov/10113/58198
Citation: Jerome-Morais, A., Wright, M.E., Liu, R., Yang, W., Jackson, M.I., Combs, G.F., Diamond, A.M. 2012. Inverse association between gluthathione peroxidase activity and both selenium-binding protein 1 levels and gleason score in human prostate tissue. The Prostate Journal. 72(9): 1006-1012. Interpretive Summary: Selenium (Se) is an essential micronutrient that is present in foodstuffs and available as a nutritional supplement. Se has demonstrated anti-cancer activity, and human epidemiological studies, cultured mammalian cells, and animal models indicate that Se prevents prostate cancer. Se is a component of a class of proteins called selenoproteins, and genotypes associated with these selenoproteins have been linked to cancer risk. Relevant to this work, glutathione peroxidase (GPX) family and Selenium-Binding Protein 1 (SBP1) are implicated in protection from tumorigenesis. In this study the relationship between Se status (blood and tissue levels), GPX or SBP1 levels and prostate cancer aggressiveness was investigated. We found that GPX activity was inversely correlated with SBP1 levels in prostate tissue in prostate cancer patients, consistent with previous observations in cell and animal experimental models. Additionally, we observed a positive correlation between prostate GPX activity and cancer aggressiveness which was statistically significant among African-Americans. This study supports the role of Se and selenoproteins in prostate cancer prevention, and might provide an explanation for the greater incidence of prostate cancer in African-Americans.
Technical Abstract: BACKGROUND. Data from human epidemiological studies, cultured mammalian cells, and animal models have supported a potentially beneficial role of selenium (Se) in prostate cancer prevention. In addition, Se-containing proteins including members of the gutathione peroxidase (GPx) family and Selenium-Binding Protein 1 (SBP1) have been linked to either cancer risk or development. For example, SBP1 levels are typically reduced in tumors compared to non-cancerous tissue, with the degree of reduction associated with increasingly poor clinical outcome. METHODS. In order to investigate inter-relationships between blood and tissue Se levels and GPx activity, tissue SBP1 levels, and disease aggressiveness using the Gleason score, we measured levels of selenium and selected selenoproteins in fasting serum and histologically normal prostate tissues obtained from 24 men undergoing radical prostatectomy for the treatment of localized prostate cancer. RESULTS. GPx enzyme activity was inversely correlated with SBP1 levels in prostate tissue as determined by densitometry of Western blots obtained using anti-SBP1 antibodies [partial Spearman’s correlation coefficients and corresponding P-values overall and in African-Americans ¼ 0.42 (0.08) and 0.53 (0.10), respectively], which is consistent with previous observations in cultured cells and mice. Of particular interest was the positive correlation between tissue GPx activity and Gleason score, with this elationship achieving statistical significance among African-Americans (r = 0.67, P = 0.02). CONCLUSION. These studies support the continued investigation of the role of Se and selenoproteins in prostate cancer prevention, development, and prognosis.