Sam68 up-regulation correlates with, and its down-regulation inhibits, proliferation and tumourigenicity of breast cancer cells
Sam68 up-regulation correlates with, and its down-regulation inhibits, proliferation and tumourigenicity of breast cancer cells
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Sam68 的上调与乳腺癌细胞的增殖和致瘤性相关，并且其下调会抑制乳腺癌细胞的增殖和致瘤性
DOI：
10.1002/path.2751
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发表时间：
2010-11-01
影响因子：
7.3
通讯作者：
Li, Mengfeng
中科院分区：
文献类型：
--
作者：
Song, Libing;Wang, Lan;Li, Mengfeng
RNA的生物合成和代谢在基因表达调控中起着重要作用。另一方面，已经表明RNA表达谱在癌症和正常细胞之间是不同的，这表明RNA代谢的异常调节可能与癌症的发展和进展相关。在目前的研究中，我们发现Sam 68，一种将细胞信号传导与RNA加工联系起来的RNA结合蛋白，在乳腺癌细胞和组织中明显过表达。免疫组化分析显示，Sam 68的表达和胞浆定位与患者的临床特征（包括临床分期、肿瘤结节转移（TNM）分类、组织学分级和ER表达）显著相关。单因素和多因素分析显示，Sam 68的表达水平和胞浆定位是影响肺癌预后的独立因素。此外，我们发现，siRNA敲低内源性Sam 68抑制乳腺癌细胞的增殖和体外致瘤性，通过阻断G1期到S期的转变。此外，我们证明了沉默Sam 68对乳腺癌细胞的抗增殖作用与细胞周期蛋白依赖性激酶抑制剂p21（CiP 1）和p27（KiP 1）的上调、FOXO因子的反式激活增强以及Akt/GSK-3 β信号转导的减弱有关。综上所述，我们的研究结果表明，Sam 68可能在促进人类乳腺癌的增殖和癌变中起重要作用，从而可能是一种新的和有用的预后标志物和人类乳腺癌治疗的潜在靶点。版权所有（C）2010大不列颠和爱尔兰病理学会。由John Wiley & Sons有限公司出版
The biosynthesis and metabolism of RNA play important roles in regulating gene expression. On the other hand, it has been shown that RNA expression profiling is differentially distinct between cancer and normal cells, suggesting the possibility that aberrant regulation of RNA metabolism might be associated with the development and progression of cancer. In the current study, we found that Sam68, an RNA-binding protein that links cellular signalling to RNA processing, was markedly overexpressed in breast cancer cells and tissues. Immunohistochemical analysis showed that the expression and cytoplasmic localization of Sam68 significantly correlated with clinical characteristics of patients, including clinical stage, tumour-nodule-metastasis (TNM) classification, histological grade, and ER expression. Univariate and multivariate analyses showed that the expression level and cytoplasmic localization of Sam68 were identified as independent prognostic factors. Furthermore, we found that siRNA knockdown of endogenous Sam68 inhibited cell proliferation and tumourigenicity of breast cancer cells in vitro, through blocking the G1 to S phase transition. Moreover, we demonstrated that the anti-proliferative effect of silencing Sam68 on breast cancer cells was associated with up-regulation of cyclin-dependent kinase inhibitor p21(CiP1) and p27(KiP1), enhanced transactivation of FOXO factors, and attenuation of Akt/GSK-3 beta signalling. Taken together, our results suggest that Sam68 might play an important role in promoting the proliferation and carcinogenesis of human breast cancer, and thereby might be a novel and useful prognostic marker and a potential target for human breast cancer treatment. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.