BCL-1--A CYCLIN/PROTO-ONCOGENE

BCL-1--细胞周期蛋白/原癌基因

• 批准号: 2084225
• 负责人: TIMOTHY C. MEEKER
• 金额: $ 6.48万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-30 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2084225
• 关键词: B lymphocyte; breast neoplasms; cell cycle; cell cycle proteins; chromosome translocation; gene expression; genetic mapping; genetically modified animals; human tissue; laboratory mouse; laboratory rabbit; lymphocytic leukemia; lymphoma; messenger RNA; molecular cloning; monoclonal antibody; natural gene amplification; neoplasm /cancer genetics; nucleic acid hybridization; nucleic acid probes; nucleic acid sequence; protooncogene; restriction mapping

In human leukemia and lymphoma, chromosome translocations disrupt adjacent proto-oncogenes, contributing to oncogenesis. The bcl-1 region on chromosome 11 has been defined as the location of breakpoints of the t(11;14)(q13:q32) translocation. This translocation has been associated with several types of B-cell lymphocytic lymphoma, including more than 50% of a common subtype called centrocytic (or intermediate) lymphoma. We have located the bcl-1 gene in this region of genomic DNA and determined it to be a member of the cyclin gene family. As such, it is likely to play an important role in cell-cycle progression. In this proposal we will finish our analysis of cDNA clones from this gene, determine its genomic structure and initiate studies to determine its function. While this proposal has great importance for the study of human leukemia and lymphoma, the bcl-1 gene may also have importance for a variety of solid cancers, including breast cancer. Evidence already exists that the bcl-1 locus from chromosome 11 is amplified in breast cancer, esophageal cancer, head and neck cancer, and others. We believe that the bcl-1 gene may be driving this amplification. therefore, it is our hypothesis that the bcl-1 gene is an important gene for several types of malignancy. More complete information about the bcl-1 gene will aid our understanding of how lymphomas and solid cancers arise. As bcl-1 is a member of the cyclin gene family, the close relationship that exists between the fields of cell-cycle control and cancer is dramatically emphasized. This raises the hope that new ways to manipulate the cell cycle will lead to additional advances in our ability to treat cancer.

在人类白血病和淋巴瘤中， 原癌基因，有助于肿瘤发生。 bcl-1基因在 11号染色体被定义为染色体断裂点的位置。 t（11;14）（q13：q32）易位。 这种易位与 与几种类型的B细胞淋巴细胞淋巴瘤，包括超过50%， 中心细胞型（或中间型）淋巴瘤的常见亚型。 我们有 将bcl-1基因定位在基因组DNA的这一区域，并确定其 成为细胞周期蛋白基因家族的一员。 因此，它可能会发挥作用， 在细胞周期进程中的重要作用。 在本提案中，我们将完成 我们分析了该基因的cDNA克隆，确定了其基因组结构， 并启动研究以确定其功能。 虽然这一建议对人类白血病的研究具有重要意义， 和淋巴瘤，bcl-1基因也可能对多种 包括乳腺癌在内的实体癌。 已有证据表明， 11号染色体的bcl-1基因座在乳腺癌、食管癌和乳腺癌中扩增， 癌症、头颈癌和其他癌症。 我们相信bcl-1基因 可能会推动这种放大。 因此，我们假设， bcl-1基因是几种恶性肿瘤的重要基因。 更多关于bcl-1基因的完整信息将有助于我们理解 淋巴瘤和实体癌是如何产生的 由于bcl-1是 细胞周期蛋白基因家族，是存在密切关系的领域 细胞周期控制和癌症的关系被极大地强调了。 这就提出 操纵细胞周期的新方法将导致更多的 癌症治疗能力的进步