BRCA1 and BRCA2 gene in breast cancer pathogenesis

BRCA1和BRCA2基因在乳腺癌发病机制中的作用

• 批准号: 6988627
• 负责人: Lawrence C 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/6988627
• 关键词: DNA repair; biological signal transduction; brca gene; breast neoplasms; cancer risk; gene expression; gene interaction; gene mutation; genetic regulation; genetic susceptibility; intermolecular interaction; karyotype; molecular pathology; neoplasm /cancer genetics; nucleic acid hybridization; ovary neoplasms; pathologic process; prostate neoplasms; protein structure function; ubiquitin; yeasts

Research in the Molecular Pathogenesis is focused on defining changes in the genes that underlie inherited susceptibilities to common diseases such as cancer and birth defects. Currently under investigation are the inherited breast and ovarian cancer genes, BRCA1 and BRCA2. The biological function of these proteins is currently unknown. Previously, we discovered which proteins specifically interact with BRCA1. In the past year we have found that BRCA1 is important for controlling the expression of other genes and is plays a role in DNA repair. Recent experiments have revealed that BRCA1 appears to help in the process of recognizing and eliminating cells that may progress to form tumors. We now know that the increase in breast, ovarian and prostate cancer risk associated with genetic variants in these genes is due to a failure of these mutated proteins to function in the DNA repair pathway. We are using yeast cells as an experimental model to test the functional consequences of mutations found in humans. We have also developed a system for identifying proteins that interact with BRCA1. It is also known that BRCA1 acts to transfer the protein ubiquitin onto other proteins. Through this action BRCA1 may be transferring a signal to start the DNA repair process. The identity of the protein to which this transfer occurs is unknown. We plan to identify these target proteins. We developed two systems capable of measuring this activity of BRCA1. If successful, these systems will allow use to identify specific proteins involved in breast tumor formation. An increased understanding of the BRCA1 and BRCA2 genes will lead to improved diagnostic procedures and possible preventative therapies.

分子发病机理中的研究集中在定义基因的变化，这些基因是遗传性疾病（例如癌症和先天缺陷）的敏感性的基因的变化。目前正在研究的是遗传性的乳腺癌和卵巢癌基因BRCA1和BRCA2。这些蛋白质的生物学功能目前尚不清楚。以前，我们发现了哪些蛋白质与BRCA1专门相互作用。在过去的一年中，我们发现BRCA1对于控制其他基因的表达很重要，并且在DNA修复中起作用。最近的实验表明，BRCA1似乎有助于识别和消除可能形成肿瘤的细胞的过程。我们现在知道，这些基因中与遗传变异有关的乳腺，卵巢和前列腺癌风险的增加是由于这些突变蛋白在DNA修复途径中起作用。我们正在使用酵母细胞作为实验模型来测试人类突变的功能后果。我们还开发了一个用于识别与BRCA1相互作用的蛋白质的系统。 众所周知，BRCA1起作用将蛋白质泛素转移到其他蛋白质上。通过这种动作，BRCA1可以传输信号以启动DNA修复过程。这种转移发生的蛋白质的身份尚不清楚。我们计划识别这些靶蛋白。我们开发了两个能够测量BRCA1活动的系统。如果成功，这些系统将允许用来鉴定参与乳腺肿瘤形成的特定蛋白质。 对BRCA1和BRCA2基因的了解将提高诊断程序和可能的预防疗法。