Regulation of ER by BRCA1 and COBRA1

BRCA1 和 COBRA1 对 ER 的调节

• 批准号: 6584810
• 负责人: SARAH E AIYAR
• 金额: $ 4.16万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6584810
• 关键词: brca gene; breast neoplasms; cancer risk; estrogen receptors; gene mutation; genetic mapping; genetic promoter element; genetic regulation; genetic transcription; immunocytochemistry; immunoprecipitation; laboratory mouse; microarray technology; neoplasm /cancer genetics; ovary neoplasms; polymerase chain reaction; postdoctoral investigator; protein protein interaction; receptor expression; tumor promoters

DESCRIPTION (provided by applicant): Breast cancer is the most common malignancy in women and approximately one in ten women in the US will develop breast cancer during her lifetime. The long-term objective of this proposal is to study how the breast cancer tumor suppressor protein, BRCA1, contributes to the prevention of familial breast and ovarian cancers. A key lacuna in our current knowledge is to understand why BRCA1 may be specific for breast and ovary tissues, since mutations in BRCA1 do not result in an increased risk for other cancers. This project will examine whether BRCA1 may be specific for breast and ovary tissues because of its role in transcriptional regulation of estrogen receptor (ER) responsive promoters. Estrogens play a pivotal role in the initiation and progression of breast tumors. We have identified a protein, COBRA1, which interacts with BRCA1 and also with ER. This project tests the hypothesis that a complex of BRCA1/COBRA1 may be recruited to ER responsive promoters to repress transcription. One aim of this proposal is to determine the functional link between COBRA1, BRCA1 and ER in transcriptional regulation. In addition, these studies will examine if COBRA1 contributes to the development of breast cancer. Understanding how COBRA1 expression influences breast cancer may provide new avenues for molecular diagnosis and treatment of breast cancers.

描述（由申请人提供）：乳腺癌是女性中最常见的恶性肿瘤，在美国大约十分之一的女性将在其一生中患上乳腺癌。本提案的长期目标是研究乳腺癌肿瘤抑制蛋白BRCA1如何促进家族性乳腺癌和卵巢癌的预防。在我们目前的知识中，一个关键的空白是理解为什么BRCA1可能对乳腺和卵巢组织具有特异性，因为BRCA1的突变不会导致其他癌症的风险增加。该项目将研究BRCA1是否因其在雌激素受体（ER）应答启动子转录调控中的作用而对乳腺和卵巢组织具有特异性。雌激素在乳腺肿瘤的发生和发展中起着关键作用。我们已经确定了一种蛋白质，COBRA1，它与BRCA1和ER相互作用。该项目验证了BRCA1/COBRA1复合体可能被招募到内质网响应启动子中抑制转录的假设。本提案的目的之一是确定COBRA1、BRCA1和ER在转录调控中的功能联系。此外，这些研究将检查COBRA1是否有助于乳腺癌的发展。了解COBRA1表达如何影响乳腺癌可能为乳腺癌的分子诊断和治疗提供新的途径。