Withers D A, Harvey R C, Faust J B, Melnyk O, Carey K, Meeker T C
Department of Medicine, University of California, San Francisco.
Mol Cell Biol. 1991 Oct;11(10):4846-53. doi: 10.1128/mcb.11.10.4846-4853.1991.
The t(11;14)(q13;q32) translocation has been associated with human B-lymphocytic malignancy. Several examples of this translocation have been cloned, documenting that this abnormality joins the immunoglobulin heavy-chain gene to the bcl-1 locus on chromosome 11. However, the identification of the bcl-1 gene, a putative dominant oncogene, has been elusive. In this work, we have isolated genomic clones covering 120 kb of the bcl-1 locus. Probes from the region of an HpaII-tiny-fragment island identified a candidate bcl-1 gene. cDNAs representing the bcl-1 mRNA were cloned from three cell lines, two with the translocation. The deduced amino acid sequence from these clones showed bcl-1 to be a member of the cyclin gene family. In addition, our analysis of expression of bcl-1 in an extensive panel of human cell lines showed it to be widely expressed except in lymphoid or myeloid lineages. This observation may provide a molecular basis for distinct modes of cell cycle control in different mammalian tissues. Activation of the bcl-1 gene may be oncogenic by directly altering progression through the cell cycle.
t(11;14)(q13;q32)易位与人类B淋巴细胞恶性肿瘤相关。已克隆出这种易位的几个实例，证明这种异常将免疫球蛋白重链基因与11号染色体上的bcl-1基因座连接起来。然而，bcl-1基因（一种假定的显性癌基因）的鉴定一直难以捉摸。在这项研究中，我们分离出了覆盖bcl-1基因座120 kb的基因组克隆。来自HpaII-微小片段岛区域的探针鉴定出一个候选bcl-1基因。从三个细胞系中克隆出代表bcl-1 mRNA的cDNA，其中两个细胞系存在这种易位。从这些克隆推导的氨基酸序列表明bcl-1是细胞周期蛋白基因家族的一员。此外，我们对大量人类细胞系中bcl-1表达的分析表明，除了在淋巴或髓系谱系中外，它在其他细胞系中广泛表达。这一观察结果可能为不同哺乳动物组织中细胞周期控制的不同模式提供分子基础。bcl-1基因的激活可能通过直接改变细胞周期进程而具有致癌性。
