Endocrine Responsiveness and Cellular Stress

内分泌反应和细胞应激

• 批准号: 8180983
• 负责人: Robert R. Clarke
• 金额: $ 96.03万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-29 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8180983
• 关键词: Affect; BCL2 gene; BCL3 gene; CAV1 gene; Cell Line; Cell Nucleus; Cells; Cellular Stress; Computer Simulation; Endocrine; Endoplasmic Reticulum; Family member; Genes; IRF1 gene; Mitochondria; Modeling; NF-kappa B; NPM1 gene; Organelles; Proteins; Rodent; Role; Seeds; Signal Transduction; Stress; functional genomics; hormone therapy; malignant breast neoplasm; microbial alkaline proteinase inhibitor; novel; response

Endocrine Responsiveness and Cellular Stress. We have identified novel signaling through the unfolded protein response (UPR) that is inifiated by an endocrine therapy-induced endoplasmic reficulum stress, with signaling further integrated through the mitochondria and nucleus. Dr. Clarke and his team will model the effects of this signaling on the function of these organelles and their respecfive roles in determining cell fate as affected by ER acfion. We will use a panel of novel cell lines, many of which we isolated [8-10,35- 42]. Inifial seed genes, e.g., API [10], BCL2 [32,33], BCL3 [49], BCLW (and other BCL2 family members), CAV1 [50], ERa [51], ERRy [10], IRF1 [27,31,52], NFKB [27,33], NPM1 [27-29], and XBP1 [27,32] will be used to initiate computational modeling of endocrine-related cell stress signals. We will extend this signaling network by including other genes known to affect endoplasmic reticulum and mitochondrial funcfion, incorporafing new targets as implicated by the functional genomics in Project 2 and the rodent studies in Project 3.

内分泌反应和细胞应激。我们通过以下方式识别了新的信号传导 由内分泌治疗诱导的内质网引发的未折叠蛋白反应（UPR） 应激，信号通过线粒体和细胞核进一步整合。克拉克博士和他的团队将 模拟这种信号传导对这些细胞器功能的影响以及它们在决定中各自的作用 细胞命运受 ER 作用的影响。我们将使用一组新的细胞系，其中许多是我们分离的 [8-10,35- 42]。初始种子基因，例如 API [10]、BCL2 [32,33]、BCL3 [49]、BCLW（和其他 BCL2 家族成员）， 将使用 CAV1 [50]、ERa [51]、ERRy [10]、IRF1 [27,31,52]、NFKB [27,33]、NPM1 [27-29] 和 XBP1 [27,32] 启动内分泌相关细胞应激信号的计算模型。我们将扩展这个信号网络 通过纳入已知影响内质网和线粒体功能的其他基因，纳入新的 项目 2 中的功能基因组学和项目 3 中的啮齿动物研究所涉及的目标。