TARGETING HEREDITARY BREAST CANCERS THROUGH ELUCIDATION OF BRCA1/2 GENE FUNCTIONS

通过阐明 BRCA1/2 基因功能靶向遗传性乳腺癌

• 批准号: 6203333
• 负责人: Stuart A Aaronson
• 金额: $ 32.78万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-24 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6203333
• 关键词: MCF7 cell; antineoplastics; antisense nucleic acid; athymic mouse; biological signal transduction; brca gene; breast neoplasms; cell cycle; clinical research; estrogens; gene expression; genetic susceptibility; human tissue; immunocytochemistry; laboratory rabbit; molecular oncology; neoplasm /cancer genetics; neoplastic cell; oncoproteins; posttranslational modifications; protein localization; radiation sensitivity; tissue /cell culture

The breast cancer susceptibility genes BRCA1 and BRCA2 account for the majority of familial breast cancers. The recent isolation of these genes by positional cloning has made it possible to investigate their functions as tumor suppressors and their impact on prognosis and treatment of breast cancer. We have generated evidence that both BRCA1 and 2 activate transcription of a specific subset of genes and have produced immunological reagents for the detection of the BRCA2 product. One major aim of this proposal is to elucidate mechanisms by which BRCA1 and 2 alter gene expression, including their interactions with other proteins. Studies in tissue culture will determine the subcellular localization of BRCA2 as well as the effects of increased or decreased expression of BRCA1 and 2 on biological responses to stress, radiation, therapeutic agents, and hormonal stimuli. Effort will also be made to establish cell lines from patients with familial breast cancer in order to characterize the effects of wild type gene expression in tumors in which BRCA1 or 2 functions have been inactivated. The knowledge gained should be useful in developing detection and treatment strategies specifically targeted to heritable breast cancers.

乳腺癌易感性基因BRCA1和BRCA2占了 大多数家族性乳腺癌。这些基因的最新隔离 通过位置克隆使研究其功能成为可能 作为肿瘤抑制剂及其对乳房预后和治疗的影响 癌症。我们已经产生了BRCA1和2激活的证据 特定基因的特定子集的转录，并产生了 用于检测BRCA2产品的免疫学试剂。一个主要 该建议的目的是阐明BRCA1和2改变的机制 基因表达，包括它们与其他蛋白质的相互作用。研究 在组织培养中将确定BRCA2的亚细胞定位为 以及BRCA1和2表达的增加或降低的影响 生物学对压力，辐射，治疗剂和 激素刺激。还将努力从 家族性乳腺癌患者为了表征 BRCA1或2功能具有的野生型基因表达 被灭活。获得的知识对于发展应该很有用 专门针对可遗传的检测和治疗策略 乳腺癌。