BCL-1--A CYCLIN/PROTO-ONCOGENE

在人类白血病和淋巴瘤中，染色体易位破坏了邻近的 原癌基因，有助于肿瘤的发生。BCL-1区域位于 11号染色体被定义为断裂点的位置 T(11；14)(q13：q32)易位。此易位已关联 与几种类型的B细胞淋巴细胞性淋巴瘤，包括50%以上 属于一种常见的亚型，称为中心性(或中间型)淋巴瘤。我们有 将bcl1基因定位在基因组DNA的这一区域，并确定它是 成为细胞周期蛋白基因家族的一员。因此，它很可能会扮演一个 在细胞周期进程中发挥重要作用。在这份提案中，我们将完成 我们对该基因的cdna克隆进行了分析，确定了其基因组结构 并开始研究以确定其功能。 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 实体癌，包括乳腺癌。已经有证据表明 11号染色体上的bcl1基因在乳腺癌、食道癌中扩增 癌症、头颈癌和其他癌症。我们认为bcl1基因 可能是这种放大效应的驱动因素。因此，我们的假设是 Bcl1基因是几种类型恶性肿瘤的重要基因。 更多关于bcl1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 Cyclin基因家族，田野之间存在的密切关系 对细胞周期控制和癌症的研究受到极大的重视。这就提高了 人们希望，操纵细胞周期的新方法将导致额外的 我们治疗癌症的能力的进步。

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.