Identification and functional evaluation of proteins controlling proliferation and differentiation of mammary epithelial cells

乳腺上皮细胞增殖分化控制蛋白的鉴定及功能评价

• 批准号: 5440326
• 负责人: Professor Dr. Bernd Groner
• 金额: --
• 依托单位: Georg-Speyer-Haus, Institut für Tumorbiologie und experimentelle Therapie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5440326?language=en
• 关键词: Identification; functional; evaluation; proteins; controlling

The mammary gland represents a uniquely suited model for the study of growth, differentiation and the control of organogenesis. We are planning to use mammary epithelial cells to identify the genes and to study the molecular mechanisms that govern their proliferation and differentiation. Since cancer formation is closely linked to aberrations of proliferation and differentiation programs, these results will also be most relevant for progress in breast cancer research. We have recently employed proteomics technology and identified new genes differentially regulated in the transition of mammary epithelial cells from a proliferation to a fully differentiated stage. These genes can be assigned to the control of RNA processing and stability, cytoskeletal organization and protein folding and stability. We now propose (1) to refine our approuch and analyse subcellular protein fractions with a new proteomics tool, (2) define the physiological funtion of interpretable candidate genes in a lactogenic hormone responsive cell culture model of mammary epithelial cells using lentiviral virus based knockdown technology and (3) verify out findings by transplantation and mammary gland reconstitution assays with genetically modified primary epithelial cells. These experiments represent a comprehensive analysis of crucial genes in mammary development and range from candidate gene identification to their functional evaluation in vitro and in vivo.

乳腺是研究生长、分化和控制器官发生的一个独特的合适模型。我们正计划使用乳腺上皮细胞来鉴定基因，并研究控制其增殖和分化的分子机制。由于癌症的形成与增殖和分化程序的异常密切相关，这些结果也将与乳腺癌研究的进展最相关。我们最近采用蛋白质组学技术，并确定了新的基因差异调节乳腺上皮细胞从增殖到完全分化阶段的过渡。这些基因可以被分配到控制RNA加工和稳定性，细胞骨架组织和蛋白质折叠和稳定性。我们现在建议（1）改进我们的方法，并使用新的蛋白质组学工具分析亚细胞蛋白质组分，（2）使用基于慢病毒的敲除技术在乳腺上皮细胞的催乳激素应答细胞培养模型中定义可解释的候选基因的生理功能，以及（3）通过遗传修饰的原代上皮细胞的移植和乳腺重建试验验证发现。这些实验代表了对乳腺发育中关键基因的全面分析，范围从候选基因鉴定到其体外和体内功能评价。