THE ROLE OF THE BRCA1 AND BRCA2 GENES IN THE PATHOGENESIS OF BREAST CANCER

BRCA1 和 BRCA2 基因在乳腺癌发病机制中的作用

• 批准号: 6290330
• 负责人: LAWRENCE BRODY
• 金额: --
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 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/6290330
• 关键词: DNA binding protein; brca gene; breast neoplasms; cancer risk; clinical research; gene expression; gene mutation; genetic susceptibility; human subject; karyotype; laboratory mouse; molecular pathology; neoplasm /cancer genetics; nucleic acid hybridization; ovary neoplasms; protein structure function

Research in the Molecular Pathogenesis is focused on defining changes in the genes that underlie inherited susceptibilities to common diseases such as cancer, heart disease and birth defects. Currently under investigation are genes involved in inherited breast and ovarian cancer. Studies are designed to better understand the function and genetics of the BRCA1 and BRCA2 genes. We have previously screened patients with familial breast and ovarian cancer for mutations in these genes. The biological function of the BRCA1 protein is currently unknown. This question is being addressed at the whole animal and biochemical level. We have purified a portion of the BRCA1 protein and used it to screen for other proteins that specifically interact with the BRCA1 protein. We have demonstrated that BRCA1 interacts with other proteins involved in chromatin remodeling and DNA repair including histone deactylase. We are currently assessing the role of this complex in tumor formation. We are also testing cell lines derived from BRCA1 and BRCA2 mutation carriers for alterations in their chromatin remodeling pathways. An increased understanding of these genes will lead to improved diagnostic procedures and possible preventative therapies. - BRCA1/2, breast cancer, genetics, Women's Health Research

分子发病机制的研究重点是确定遗传易感性的基因变化，如癌症、心脏病和出生缺陷。目前正在研究的是与遗传性乳腺癌和卵巢癌有关的基因。研究的目的是更好地了解BRCA1和BRCA2基因的功能和遗传学。我们之前对家族性乳腺癌和卵巢癌患者进行了这些基因突变的筛查。BRCA1蛋白的生物学功能目前尚不清楚。这个问题是在整个动物和生物化学水平上解决的。我们纯化了BRCA1蛋白的一部分，并用它来筛选与BRCA1蛋白特异性相互作用的其他蛋白质。我们已经证明BRCA1与其他参与染色质重塑和DNA修复的蛋白质相互作用，包括组蛋白去乙酰化酶。我们目前正在评估这种复合物在肿瘤形成中的作用。我们也在测试来自BRCA1和BRCA2突变携带者的细胞系，以了解其染色质重塑途径的改变。增加对这些基因的了解将导致改进诊断程序和可能的预防性治疗。- BRCA1/2，乳腺癌，遗传学，妇女健康研究