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通过表达谱分析比较基因工程小鼠乳腺癌模型与人类乳腺癌

Comparing genetically engineered mouse mammary cancer models with human breast cancer by expression profiling.

作者信息

Shoushtari Alexander N, Michalowska Aleksandra M, Green Jeffrey E

机构信息

Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

出版信息

Breast Dis. 2007;28:39-51. doi: 10.3233/bd-2007-28105.

Abstract

Breast cancer is a heterogeneous disease, and much of the molecular basis for this heterogeneity is being unraveled using advanced genomic technologies. More recently, global transcriptional profiling has proven to be an effective new tool for characterizing human tumors. Genomic "signatures'' have been developed that classify tumors with varying prognoses and responses to treatment. Recent studies have begun to extend the use of global transcriptional profiling to better characterize genetically engineered mouse (GEM) models of breast cancer, which will improve the ability to translate basic research advances into clinical advances. GEM models of mammary carcinoma have proven to be invaluable tools to gain insight into mechanisms underlying tumor initiation, progression, and therapeutic responses in an in vivo system where tumors spontaneously develop in an appropriate tissue environment. This review will discuss the use of transcriptional profiling of breast cancer in tumors from both human patients and GEM models to improve prognostic measures, examine mechanisms of tumor initiation and progression, identify novel therapeutic targets, and improve pre-clinical testing for drug development. Together, these advances offer a framework for classifying human tumors, identifying appropriate GEM models for specific experimental purposes, and utilizing the combined data to identify more specific and effective cancer therapies.

摘要

乳腺癌是一种异质性疾病,利用先进的基因组技术正在揭示这种异质性的许多分子基础。最近,全基因组转录谱分析已被证明是一种表征人类肿瘤的有效新工具。已经开发出基因组“特征”,用于对具有不同预后和治疗反应的肿瘤进行分类。最近的研究已开始将全基因组转录谱分析的应用范围扩大,以更好地表征乳腺癌的基因工程小鼠(GEM)模型,这将提高将基础研究进展转化为临床进展的能力。事实证明,乳腺癌的GEM模型是非常宝贵的工具,可用于深入了解肿瘤在合适的组织环境中自发发生的体内系统中肿瘤起始、进展和治疗反应的潜在机制。本综述将讨论对人类患者肿瘤和GEM模型中的乳腺癌进行转录谱分析,以改善预后评估、研究肿瘤起始和进展机制、识别新的治疗靶点以及改进药物开发的临床前测试。总之,这些进展为人类肿瘤分类、为特定实验目的识别合适的GEM模型以及利用综合数据识别更特异和有效的癌症治疗方法提供了一个框架。

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