Super-activity of gene regulators in fibrosarcoma

纤维肉瘤中基因调节因子的超活性

• 批准号: 7052646
• 负责人: Abigail E Kroch
• 金额: $ 4.6万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-31 至 2009-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7052646
• 关键词: genes; neoplasm /cancer; receptor

DESCRIPTION (provided by applicant): Intracellular receptor (IR) activities dramatically increase at the final transition to the tumor cell in the mouse model for human sarcoma. Although the changes in receptor function are not likely to be the cause of cancer, they may be "passive bystanders" that are markers of a cellular alteration that may effect both the "super-activation" of the receptors and the cancer progression. In this study, we will focus on the pattern of changes in activity of the glucocorticoid receptor (GR) in cell lines that represent aggressive fibromatosis (the last pre-tumor stage) and the fibrosarcoma tumor. GR binds to specific genomic glucocorticoid response elements and triggers assembly of multicomponent, response element-specific regulatory complexes. We will define patterns of functional surfaces on GR, seeking patterns that correlate with super-activation. In addition, we shall determine the relationship between GRE sequences, GR-DNA affinities, and GR- coactivator recruitment in super-activated genes. These studies will facilitate a better understanding of cancer as a regulatory transition, and of the structure, mechanism and selectivity of cellular regulatory pathways.

描述（由申请方提供）：在人肉瘤小鼠模型中，细胞内受体（IR）活性在最终转化为肿瘤细胞时显著增加。虽然受体功能的变化不太可能是癌症的原因，但它们可能是“被动旁观者”，是可能影响受体的“超激活”和癌症进展的细胞改变的标志物。在这项研究中，我们将集中在糖皮质激素受体（GR）的活性变化的模式在细胞系，代表侵略性纤维瘤病（最后的肿瘤前阶段）和纤维肉瘤肿瘤。GR与特定的基因组糖皮质激素反应元件结合，并触发多组分反应元件特异性调节复合物的组装。我们将定义GR功能表面的模式，寻找与超激活相关的模式。此外，我们将确定GRE序列之间的关系，GR-DNA亲和力，和GR-共激活剂招募超活化基因。这些研究将有助于更好地理解癌症作为一种调节过渡，以及细胞调节途径的结构，机制和选择性。