Department of Molecular & Cellular Biology, BCM130, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Breast Cancer Res Treat. 2012 Nov;136(1):253-65. doi: 10.1007/s10549-012-2262-7. Epub 2012 Sep 27.
Silencing mediator of retinoic acid and thyroid hormone receptor (SMRT), also known as nuclear corepressor 2 (NCOR2) is a transcriptional corepressor for multiple members of the nuclear receptor superfamily of transcription factors, including estrogen receptor-α (ERα). In the classical model of corepressor action, SMRT binds to antiestrogen-bound ERα at target promoters and represses ERα transcriptional activity and gene expression. Herein SMRT mRNA and protein expression was examined in a panel of 30 breast cancer cell lines. Expression of both parameters was found to vary considerably amongst lines and the correlation between protein and mRNA expression was very poor (R (2) = 0.0775). Therefore, SMRT protein levels were examined by immunohistochemical staining of a tissue microarray of 866 patients with stage I-II breast cancer. Nuclear and cytoplasmic SMRT were scored separately according to the Allred score. The majority of tumors (67 %) were negative for cytoplasmic SMRT, which when detected was found at very low levels. In contrast, nuclear SMRT was broadly detected. There was no significant difference in time to recurrence (TTR) according to SMRT expression levels in the ERα-positive tamoxifen-treated patients (P = 0.297) but the difference was significant in the untreated patients (P = 0.01). In multivariate analysis, ERα-positive tamoxifen-untreated patients with high nuclear SMRT expression (SMRT 5-8, i.e., 2nd to 4th quartile) had a shorter TTR (HR = 1.94, 95 % CI, 1.24-3.04; P = 0.004) while there was no association with SMRT expression for ERα-positive tamoxifen-treated patients. There was no association between SMRT expression and overall survival for patients, regardless of whether they received tamoxifen. Thus while SMRT protein expression was not predictive of outcome after antiestrogen therapy, it may have value in predicting tumor recurrence in patients not receiving adjuvant tamoxifen therapy.
视黄酸和甲状腺激素受体沉默调节因子（SMRT），也称为核受体共抑制因子 2（NCOR2），是核受体转录因子超家族的多个成员的转录共抑制因子，包括雌激素受体-α（ERα）。在经典的共抑制因子作用模型中，SMRT 与抗雌激素结合的 ERα 在靶启动子上结合，并抑制 ERα 转录活性和基因表达。在此，在 30 个乳腺癌细胞系的面板中检查了 SMRT mRNA 和蛋白表达。发现两种参数在细胞系之间变化很大，并且蛋白和 mRNA 表达之间的相关性非常差（R（2）= 0.0775）。因此，通过对 866 例 I-II 期乳腺癌患者的组织微阵列进行免疫组织化学染色来检查 SMRT 蛋白水平。根据 Allred 评分分别对核和细胞质 SMRT 进行评分。大多数肿瘤（67％）细胞质 SMRT 阴性，当检测到 SMRT 时，其水平非常低。相比之下，核 SMRT 广泛存在。在接受他莫昔芬治疗的 ERα 阳性患者中，根据 SMRT 表达水平，无复发生存时间（TTR）无显著差异（P = 0.297），但在未治疗的患者中差异显著（P = 0.01）。在多变量分析中，高核 SMRT 表达（SMRT 5-8，即第 2 至第 4 四分位数）的 ERα 阳性未经他莫昔芬治疗的患者 TTR 较短（HR = 1.94，95％CI，1.24-3.04；P = 0.004），而 ERα 阳性接受他莫昔芬治疗的患者则与 SMRT 表达无关。SMRT 表达与患者的总生存无关，无论他们是否接受他莫昔芬治疗。因此，虽然 SMRT 蛋白表达不能预测抗雌激素治疗后的结局，但它可能对预测未接受辅助他莫昔芬治疗的患者的肿瘤复发有价值。
