Animal Models

PPG的中心目标是了解细胞运动和侵袭，其重点是细胞内的 肿瘤微环境中的相互作用。这些相互作用只能在小鼠中有效建模， 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）的假设的重要性，特别是信号 分子在肿瘤侵袭和转移过程中的作用核心产生基因操纵的 小鼠，并提供了许多研究者使用的技术，包括乳腺肿瘤的分期， 乳房脂肪垫移植、肺转移测定和静脉内注射。PPG已经 开创了肿瘤内不同细胞类型的活体成像。这就要求各个血统 用谱系特异性启动子表达的荧光蛋白标记。为了确定这两个巨噬细胞的年龄， 用GFP或CFP标记内皮细胞和肿瘤细胞，并将这些菌株中的每一种与 乳腺肿瘤荷瘤小鼠。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。如此大规模的老鼠繁殖 任何一个实验室都做不到。此外，如果没有这个核心，该项目的许多成员 细胞生物学家和生物化学家，会发现很难将他们的基本原理 在培养的细胞中观察到关于它们在体内肿瘤进展中的作用的可检验的假设。 具体目标是： 1)开发和维持小鼠，其中多个细胞谱系通过表达荧光标记。 proteins.这些在MMTV-Polyoma和Her 2/Neu乳腺肿瘤荷瘤小鼠上进行。 2)以与PPG相关的方式对小鼠基因组进行遗传操作，并开发方法， 有条件地消除单个细胞谱系中的特定基因。 3)在肿瘤分期和转移检测方面提供帮助。 4)提供与PPG相关的其他技术，如骨髓移植;乳房 移植、转基因和基因靶向构建建议。 乳腺癌是欧洲和美国妇女最常见的癌症， mortality.我们的研究表明，肿瘤微环境的调节在肿瘤的发生发展中起着重要的作用， 转移细胞之间的这种复杂相互作用只能在小鼠中建模。从这些中获得的见解 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.