Evidence that selenium binding protein 1 is a tumor suppressor in prostate cancer.
Evidence that selenium binding protein 1 is a tumor suppressor in prostate cancer.
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DOI：
10.1371/journal.pone.0127295
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Diamond AM
中科院分区：
文献类型：
--
作者：
Ansong E;Ying Q;Ekoue DN;Deaton R;Hall AR;Kajdacsy-Balla A;Yang W;Gann PH;Diamond AM
硒结合蛋白 1（SBP1、SELENBP1、hSP56）是一种硒相关蛋白，在肿瘤中水平较低，其较低水平通常预示着不良的临床结果。区分惰性前列腺癌和侵袭性前列腺癌是疾病管理的主要挑战。研究人员通过双重免疫荧光成像研究了 SBP1 水平、肿瘤分级和前列腺切除术后疾病复发之间的关联，该组织微阵列包含 202 名在前列腺切除术后经历生化 (PSA) 复发的前列腺癌患者和 202 名癌症未复发的匹配对照患者的组织。样本按年龄、种族、病理阶段和格里森分级进行匹配，并使用 Vectra 多光谱成像系统对图像进行量化。荧光标记针对 SBP1 和细胞角蛋白 8/18，以限制对肿瘤细胞的评分，并对细胞核和细胞质中的 SBP1 进行逐个细胞定量。使用线性回归分析，核 SBP1 水平和核质比与肿瘤分级呈负相关。根据对照中的 SBP1 水平将样本分类为四分位数后，最低四分位数的肿瘤复发的可能性是任何其他四分位数的肿瘤的两倍以上。诱导性异位 SBP1 表达降低了 HCT-116 人类肿瘤细胞在软琼脂中生长的能力（一种转化的衡量标准），但不影响增殖。表达 SBP1 的细胞还表现出对 p53 肿瘤抑制因子丝氨酸 15 磷酸化的强烈诱导。这些数据表明，SBP1 的缺失可能在前列腺癌进展中发挥独立的贡献作用，并且其水平可能有助于区分惰性疾病和侵袭性疾病。
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.
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