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The role of Chromosome translocation-related genes on tumorigenecity in hematological malignancie

染色体易位相关基因在血液恶性肿瘤致瘤中的作用

基本信息

批准号：
06671119
负责人：
AKAO Yukihiro
金额：
$ 1.22万
依托单位：
Osaka Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671119/
关键词：
Chromosome 11q23 Chromosome translocation Leukemia Malignant lymhoma RCK MLL bcl-2蛋白アポトーシス

项目摘要

The chromosome translocations ocurring at chromosome 11 band q23 (11q23) are identified as a nonrandam cytogenetic event in various kinds of leukemias and lymphomas. We cloned the breakpoints of t (11 ; 14) (q23 ; q32) in B-cell lymphoma and t (11 ; 19) (q123 ; p13) in an infantile leukemia and identified the target genes on 11q23, RCK and MLL,respectively. The RCK gene product is a member of DEAD box protein/RNA helicase family. Expression of the RCK gene was studied by Northern and Western blot analyzes. By Northern blot analysis, a 7.5 kb transcript of the RCK gene was shown to be expressed ubiquitously in human and mouse tissues. Polyclonal antibodies against RCK gene product were raised and RCK gene expression pattern was examined in human and mouse tissues. Two different polyclonal antirck antibodies detected a specific 54-kilodalton product named rck/p54 in the majority of human and mouse tissues tested by Western blot analysis. However, rck/p54 was shown to be very low in the human brain and was not detectable in lumbar muscle and lung tissues. Interestingly, malignant transformed human cells arising from the tissues with low or no expression of rck/p54, such as neuroblastoma, glioblastoma, rhabdomyosarcoma and lung cancer cell lines produced a moderate amount of rck/p54 protein, suggesting that rck/p54 plays a role on tumorigenesis.On the other hand, the MLL of 15 kb transcript was shown to be homologous to the tritrax gene of Drosophila, which is a transcription factor, and involved in vast major 11q23 translocations of leukemias. We also demonstrated that the chimeric MLL transcripts are found in all cases and the breakpoints are localized to the 3' side of the zink finger region.

发生于第11号染色体q23带（11 q23）的染色体易位是各种白血病和淋巴瘤中的非随机细胞遗传学事件。我们克隆了B细胞淋巴瘤t（11 ; 14）（q23 ; q32）和婴儿白血病t（11 ; 19）（q123 ; p13）的断裂点，并分别鉴定了11 q23、RCK和MLL上的靶基因。RCK基因产物是DEAD box蛋白/RNA解旋酶家族的成员。通过北方和Western印迹分析研究RCK基因的表达。通过北方印迹分析，显示RCK基因的7.5 kb转录物在人和小鼠组织中普遍表达。制备抗RCK基因产物的多克隆抗体，检测RCK基因在人和小鼠组织中的表达模式。两种不同的多克隆抗rck抗体检测到一个特定的54千道尔顿的产品命名为rck/p54在大多数的人类和小鼠组织的Western印迹分析测试。然而，rck/p54在人脑中被证明是非常低的，并且在腰肌和肺组织中检测不到。有趣的是，在rck/p54低表达或不表达的组织中产生的恶性转化细胞，如神经母细胞瘤、胶质母细胞瘤、横纹肌肉瘤和肺癌细胞系，产生中等量的rck/p54蛋白，提示rck/p54在肿瘤发生中起作用。它是一种转录因子，并参与白血病的大量主要11 q23易位。我们还证明了在所有情况下都发现了嵌合MLL转录物，并且断裂点位于锌指区的3'侧。