SIRT2: Tumour suppressor or tumour promoter in operable breast cancer?
SIRT2: Tumour suppressor or tumour promoter in operable breast cancer?
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DOI：
10.1016/j.ejca.2013.10.005
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发表时间：
2014-01-01
影响因子：
8.4
通讯作者：
Shiels, Paul G.
中科院分区：
文献类型：
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作者：
McGlynn, Liane M.;Zino, Samer;Shiels, Paul G.
目的：Sirtuins是一个参与细胞应激、存活和损伤反应的基因家族。它们与包括癌症在内的一系列疾病有关，与它们在肿瘤发生中的功能有关的大多数信息来自体外研究或模式生物。它们作为肿瘤抑制剂或肿瘤促进剂的假定作用仍有待于体内验证。关于它们在乳腺肿瘤发生中的作用知之甚少。我们试图评估7 sirtuin家族成员（SIRT 1 -7）在人类乳腺癌队列中，在临床病理特征和疾病的结果。材料和方法：SIRT 1 -7蛋白水平的免疫组织化学分析进行了392雌激素受体（ER + VE）和153 ER-VE乳腺肿瘤样本。使用相对定量真实的时间PCR评估正常（n = 25）、非恶性（n = 73）和恶性（n = 70）乳腺组织中的SIRT 1 -7转录水平。统计分析确定是否SIRT 1 -7转录或蛋白表达与临床参数或outcome.Results：在ER-ve肿瘤，高蛋白水平的核SIRT 2与减少复发时间和疾病特异性死亡相关。这种关联仅在3级肿瘤中观察到。在ER+ve队列中，在3级肿瘤患者中，高SIRT 2核水平与他莫昔芬治疗期间较短的无病生存期和复发时间相关。相反，在2级肿瘤，高SIRT 2水平与增加的时间recurrent.Conclusions：我们的数据表明，SIRT 2是sirtuin主要参与乳腺肿瘤的发生和预后。这表明SIRT 2作为肿瘤抑制剂或肿瘤促进剂，取决于乳腺肿瘤的分级。(C)2013爱思唯尔有限公司保留所有权利。
Purpose: Sirtuins comprise a family of genes involved in cellular stress, survival and damage responses. They have been implicated in a range of diseases including cancer, with most information pertaining to their function in tumourigenesis being derived from in vitro studies, or model organisms. Their putative roles as tumour suppressors or tumour promoters remain to be validated in vivo. Little is known about their role in breast tumourigenesis. We sought to evaluate the seven sirtuin family members (SIRT1-7) in a human breast cancer cohort, in relation to clinico-pathological features and outcome of the disease.Materials and methods: Immunohistochemical analysis of SIRT1-7 protein levels was undertaken in 392 oestrogen receptor (ER + ve) and 153 ER-ve breast tumour samples. SIRT1-7 transcriptional levels were assessed in normal (n = 25), non-malignant (n = 73) and malignant (n = 70) breast tissue using Relative Quantitative Real Time PCR. Statistical analyses determined if SIRT1-7 transcription or protein expression was associated with clinical parameters or outcome.Results: In ER-ve tumours, high protein levels of nuclear SIRT2 were associated with reduced time to recurrence and disease-specific death. This association was only observed in Grade 3 tumours. In the ER+ve cohort, high SIRT2 nuclear levels were associated with shorter disease-free survival and time to recurrence whilst on Tamoxifen, in patients with Grade 3 tumours. Conversely, in Grade 2 tumours, high SIRT2 levels were associated with increased time to recurrence.Conclusions: Our data suggest that SIRT2 is the sirtuin predominantly involved in breast tumourigenesis and prognosis. It indicates that SIRT2 acts as a tumour suppressor or tumour promoter dependent upon breast tumour grade. (C) 2013 Elsevier Ltd. All rights reserved.