Transcriptional Activation by Glucocorticoid and Progesterone Receptors

糖皮质激素和孕酮受体的转录激活

• 批准号: 6432405
• 负责人: TREVOR K ARCHER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6432405
• 关键词: DNA footprinting; breast neoplasms; chromatin; corticosteroid receptors; gene expression; genetic transcription; glucocorticoids; hormone receptor; immunoprecipitation; progesterone; progesterone receptors; progestins

During FY2000 we built upon key observations that we made concerning the mechanisms by which steroid receptors activate transcription within breast cancer cells. We demonstrated that proteins involved in the manipulation of chromatin structure, so called chromatin remodeling machines, represent the key components in the cascade of events that results in the activation of the genetic program in human breast cancer cells. We have analyzed the activity of the glucocorticoid receptor within breast and Osteosacoma cancer cells that differ in the expression of components of the chromatin remodeling machines. These cells display an altered response to a variety of clinically important hormone antagonist and will be useful in evaluating various anti-hormone strategies in breast cancer. In addition they are a unique resource to evaluate and characterize the impact of a number of environmental agents in human cells. To this end we have continued to develop methodologies that allow us to look a protein-DNA interactions within living cells,in vivo footprinting, as well as changes at the control regions of specific genes within living cell, chromatin immunoprecipitation (CHIP) assays.

在2000财政年度，我们建立了关于类固醇受体激活乳腺癌细胞内转录的机制的关键观察结果。 我们证明了参与染色质结构操纵的蛋白质，即所谓的染色质重塑机器，代表了导致人类乳腺癌细胞遗传程序激活的级联事件中的关键组成部分。我们已经分析了乳腺癌和骨肉瘤癌细胞内糖皮质激素受体的活性，这两种癌细胞在染色质重塑机器的组分表达上不同。这些细胞显示出对各种临床上重要的激素拮抗剂的反应改变，并将有助于评估乳腺癌中的各种抗激素策略。 此外，它们是评估和表征许多环境因子对人类细胞影响的独特资源。为此，我们继续开发方法，使我们能够观察活细胞内的蛋白质-DNA相互作用，体内足迹，以及活细胞内特定基因控制区的变化，染色质免疫沉淀（CHIP）测定。