title: Evidence that selenium binding protein 1 is a tumor suppressor in prostate cancer.
abstract: Selenium-Binding Protein 1 (SBP1, SELENBP1, hSP56) is a selenium-associated protein shown to be at lower levels in tumors, and its lower levels are frequently predictive of a poor clinical outcome. Distinguishing indolent from aggressive prostate cancer is a major challenge in disease management. Associations between SBP1 levels, tumor grade, and disease recurrence following prostatectomy were investigated by duplex immunofluorescence imaging using a tissue microarray containing tissue from 202 prostate cancer patients who experienced biochemical (PSA) recurrence after prostatectomy and 202 matched control patients whose cancer did not recur. Samples were matched by age, ethnicity, pathological stage and Gleason grade, and images were quantified using the Vectra multispectral imaging system. Fluorescent labels were targeted for SBP1 and cytokeratins 8/18 to restrict scoring to tumor cells, and cell-by-cell quantification of SBP1 in the nucleus and cytoplasm was performed. Nuclear SBP1 levels and the nuclear to cytoplasm ratio were inversely associated with tumor grade using linear regression analysis. Following classification of samples into quartiles based on the SBP1 levels among controls, tumors in the lowest quartile were more than twice as likely to recur compared to those in any other quartile. Inducible ectopic SBP1 expression reduced the ability of HCT-116 human tumor cells to grow in soft agar, a measure of transformation, without affecting proliferation. Cells expressing SBP1 also demonstrated a robust induction in the phosphorylation of the p53 tumor suppressor at serine 15. These data indicate that loss of SBP1 may play an independent contributing role in prostate cancer progression and its levels might be useful in distinguishing indolent from aggressive disease.
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Ansong
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, United States of America; College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China; Department of Pathology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ying
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Dede N
authors.initials: DN
authors.lastname: Ekoue
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Ryan
authors.initials: R
authors.lastname: Deaton
authors.affiliation: University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Hall
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Andre
authors.initials: A
authors.lastname: Kajdacsy-Balla
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, United States of America; Department of Pathology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Wancai
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Gann
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Diamond
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D051137:Selenium-Binding Proteins / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C495175:SELENBP1 protein, human; D051137:Selenium-Binding Proteins