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乳腺癌中抑制元件 1(RE-1)-沉默转录因子(REST)的表达和功能。

Expression and functions of the repressor element 1 (RE-1)-silencing transcription factor (REST) in breast cancer.

机构信息

Department of Pathology, Xiangya School of Medicine, Central South University, Changsha, Hunan, PR China.

出版信息

J Cell Biochem. 2010 Jul 1;110(4):968-74. doi: 10.1002/jcb.22610.

Abstract

The repressor element 1 (RE-1)-silencing transcription factor (REST), also known as the neuron-restrictive silencer factor (NRSF) or repressor binding to the X2 box (XBR), REST/NRSF/XBR, is originally discovered as a transcriptional repressor of a large number of primarily terminal neuronal differentiation genes in non-neuronal cells and neural stem cells (NSCs). Recently, the tumor-suppressor function of REST is finally proved. However, the expression profile and function of REST in breast cancer are not very clear. In this study, the expression of REST was detected in breast cancer tissue by immunohistochemistry. The results showed that REST expression was significantly lower in breast cancer samples compared to normal and benign breast samples (P < 0.05). Furthermore, the shRNA approach was used to investigate the function of REST in human breast cancer cells. Knocking down REST expression by shRNA in the human breast cancer MCF-7 cells resulted in an increase in cell proliferation, suppression in apoptosis, and reduced sensitivity to anticancer drug with a concurrent significantly up-regulated expression of Bcl-2. These data implied a significant role of REST in breast cancer. The reduced expression of REST might contribute to the breast cancer pathogenesis.

摘要

阻遏元件 1(RE-1)-沉默转录因子(REST),也称为神经元限制沉默因子(NRSF)或 X2 盒结合抑制因子(XBR),最初在非神经元细胞和神经干细胞(NSC)中被发现是许多主要终末神经元分化基因的转录抑制剂。最近,REST 的肿瘤抑制功能终于得到证实。然而,REST 在乳腺癌中的表达谱和功能尚不清楚。在本研究中,通过免疫组织化学检测乳腺癌组织中 REST 的表达。结果表明,与正常和良性乳腺样本相比,乳腺癌样本中 REST 的表达显著降低(P<0.05)。此外,还使用 shRNA 方法研究了 REST 在人乳腺癌细胞中的功能。在人乳腺癌 MCF-7 细胞中通过 shRNA 敲低 REST 的表达导致细胞增殖增加,凋亡抑制,对抗癌药物的敏感性降低,同时 Bcl-2 的表达显著上调。这些数据表明 REST 在乳腺癌中具有重要作用。REST 的表达降低可能有助于乳腺癌的发病机制。

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