Animal Models

PPG的中心目标是了解细胞的运动和侵袭，其重点是细胞 肿瘤微环境中的相互作用。这些相互作用只能在小鼠和 核心C提供了获得乳腺癌小鼠模型的途径。它允许快速测试(在 小鼠育种和遗传操作)关于特定信号重要性的假说 肿瘤侵袭和转移过程中的分子。核心产生了基因操纵的 并提供了许多研究人员使用的技术，包括乳腺肿瘤的分期， 乳房脂肪垫移植、肺转移检测和静脉注射。PPG已经 开创了肿瘤内不同细胞类型的活体成像技术。这需要个人血统来 用谱系特异性启动子表达的荧光蛋白进行标记。为了确定两个巨噬细胞的年龄， 血管内皮细胞和肿瘤细胞用绿色荧光蛋白或绿色荧光蛋白标记，每个菌株与 荷瘤小鼠。核心C维持所有这些菌落并进行多次杂交， 提供基因分型和菌落维护服务。如此大规模的老鼠饲养将是 对任何一个实验室来说都是不可能的。此外，如果没有这个核心，项目的许多成员 程序是细胞生物学家和生物化学家，他们会发现很难翻译他们的基本原理 在培养细胞中的观察转化为关于它们在体内肿瘤进展中的作用的可检验的假说。 具体目标是： 1)建立和维持以荧光表达为标志的多种细胞系的小鼠 蛋白质。在MMTV-多发性瘤和Her2/Neu乳腺肿瘤荷瘤小鼠身上都进行了这些研究。 2)以与PPG相关的方式对小鼠基因组进行基因操作，并开发方法学以 有条件地去除单个细胞系中的特定基因。 3)为肿瘤分期和转移分析提供帮助。 4)提供与PPG相关的其他技术，如骨髓移植、乳房 移植、转基因和基因打靶构建建议。 乳腺癌是欧洲和美国妇女最常见的癌症，发病率很高， 死亡率。我们的研究表明，肿瘤微环境的调节具有重要作用。 转移。细胞之间的这种复杂的相互作用只能在小鼠身上建模。从这些方面获得的洞察力 研究应该有助于开发抑制转移的治疗方法。

The PPG has as its central aim the understanding of cell motility and invasion with its focus upon cellular interactions in the tumor microenvironment. These interactions can only be effectively modeled in mice and Core C provides access to mouse models of breast cancer. It allows the rapid testing (in the context of mouse breeding and genetic manipulation) of hypotheses about the importance of particular signaling molecules in the process of tumor invasion and metastasis.. The core generates genetically manipulated mice and provides access to techniques used by many investigators including, staging of mammary tumors, mammary fat pad transplantation, lung metastasis assays and intravenous injections. The PPG has pioneered the intravital imaging of different cell types within the tumor. This requires individual lineages to be marked with fluorescent proteins expressed from lineage specific promoters. To date both macrophages, endothelial and tumor cells are labeled with GFP or CFP and each of these strains are crossed with mammary tumor bearing mice. Core C maintains all these colonies and performs the multiple crosses, providing genotyping and colony maintenance services. Such large-scale mouse breeding would be impossible for any one laboratory. Furthermore, without this core, many of the members of the project program who are cell biologists and biochemists, would find it very difficult to translate their fundamental observations in cultured cells into testable hypotheses about their role in tumor progression in vivo. The specific aims are: 1) Develop and maintain mice in which multiple cell lineages are marked by expression of fluorescent proteins. These are carried on both the MMTV-Polyoma and Her2/Neu mammary tumor-bearing mice. 2) Genetically manipulate the mouse genome in ways relevant to the PPG and develop methodology to conditionally ablate specific genes in individual cell lineages. 3) Provide assistance in tumor staging and metastasis assays. 4) Provide other techniques relevant to the PPG such as bone marrow transplantation; mammary transplantation, transgenic and gene targeting construct advice. Breast cancer is the most common cancer of women in Europe and the US causing great morbidity and mortality. Our studies have indicated an important role for the tumor microenvironment modulating metastasis. This complex interaction between cells can only be modeled in mice. Insight gained form these studies should help in the development of therapeutics that inhibit metastasis.