Core--Transgenic and Embryonic Stem Cell

核心--转基因和胚胎干细胞

• 批准号: 6995157
• 负责人: MICHAEL L ROBINSON
• 金额: $ 15.19万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6995157
• 关键词: biomedical facility; breast neoplasms; cell cell interaction; embryonic stem cell; fibroblasts; genetically modified animals; laboratory mouse; mammary epithelium; neoplastic growth

Cancer is often the result of a complex set of genetic alterations that give aberrant cells the ability to undergo deregulated growth. Several different genetic alterations in mice have been shown to increase the incidence of tumor formation, but even in these cases, only subsets of cells within the organism give rise to tumors indicating that genetic changes beyond the initial insult are required to progress to tumor formation. We hypothesize that genetic changes in both the epithelial and mesenchymal compartments of the breast contribute to the initiation, growth and/or metastasis of breast cancer. The Transgenic and Embryonic Stem Cell (TG/ES) Core seeks to integrate the efforts of several investigators working to explore epithelial and stromal interactions and contributions leading to mammary carcinogenesis. The TG/ES Core has several specific goals related to the mammary oncogenesis project. The first of these goals is to develop transgenic mouse strains expressing Cre recombinase targeted to the mammary stromal fibroblasts under the influence of tissue-specific and inducible promoters. The TG/ES Core will also produce, import, rederive, distribute and cryopreserve strains of mice necessary to carry out individual Projects in the Program Project Grant. These include mice expressing Cre recombinase in the mammary epithelium and various mice carrying conditional (LoxP flanked) mutations detailed in individual Projects within the Program Project Grant.

癌症通常是一组复杂的基因改变的结果，这些基因改变使异常细胞能够进行失控的生长。小鼠中的几种不同的遗传改变已被证明会增加肿瘤形成的发生率，但即使在这些情况下，也只有生物体内的细胞亚群会引起肿瘤，这表明需要超过初始损伤的遗传改变才能进展到肿瘤形成。我们假设乳腺上皮和间充质细胞的遗传变化有助于乳腺癌的发生、生长和/或转移。 转基因和胚胎干细胞（TG/ES）核心旨在整合几位研究人员的努力，以探索上皮和基质的相互作用和导致乳腺癌发生的贡献。TG/ES核心有几个与乳腺肿瘤发生项目相关的具体目标。这些目标中的第一个是开发在组织特异性和诱导型启动子的影响下表达靶向乳腺基质成纤维细胞的Cre重组酶的转基因小鼠品系。TG/ES核心还将生产、进口、再衍生、分发和冷冻保存必要的小鼠品系，以执行计划项目赠款中的各个项目。这些包括在乳腺上皮中表达Cre重组酶的小鼠和携带条件性（LoxP侧翼）突变的各种小鼠，这些突变在计划项目资助内的各个项目中详细描述。