Sakamoto Kazuhito, Schmidt Jeffrey W, Wagner Kay-Uwe
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE, 68198-5950, USA,
Methods Mol Biol. 2015;1267:47-71. doi: 10.1007/978-1-4939-2297-0_3.
Breast cancer is the most common cause of cancer death in women worldwide. This malignancy is a complex disease, which is defined by an intrinsic heterogeneity on the histopathological and molecular level as well as response to therapy and outcome. In addition to classical histopathological features, breast cancer can be categorized into at least five major subtypes based on comprehensive gene expression profiling: luminal A, luminal B, basal-like, ERBB2-positive, and normal-like breast cancer. Genetically engineered mouse models can serve as tools to study the molecular underpinnings for this disease. Given the genetic complexity that drives the initiation and progression of individual breast cancer subtypes, it is evident that certain models can reflect only particular aspects of this malignancy. In this book chapter, we will primarily focus on advances in modeling breast cancer at defined stages of carcinogenesis using genetically engineered mice. We will discuss the ability as well as shortcomings of these models to faithfully recapitulate the spectrum of human breast cancer subtypes.
乳腺癌是全球女性癌症死亡的最常见原因。这种恶性肿瘤是一种复杂的疾病，其在组织病理学和分子水平上具有内在异质性，并且在对治疗的反应和预后方面也存在差异。除了经典的组织病理学特征外，基于全面的基因表达谱分析，乳腺癌可至少分为五种主要亚型：腔面A型、腔面B型、基底样型、ERBB2阳性型和正常样型乳腺癌。基因工程小鼠模型可作为研究这种疾病分子基础的工具。鉴于驱动个体乳腺癌亚型发生和发展的遗传复杂性，显然某些模型只能反映这种恶性肿瘤的特定方面。在本章中，我们将主要关注使用基因工程小鼠在致癌作用的特定阶段对乳腺癌进行建模的进展。我们将讨论这些模型忠实地再现人类乳腺癌亚型谱的能力以及不足之处。
