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Functional analysis of cyclin D1 alternative transcript b

cyclin D1替代转录物b的功能分析

基本信息

批准号：
10670980
负责人：
HOSOKAWA Yoshitaka
金额：
$ 2.37万
依托单位：
AICHI CANCER CENTER
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

The cyclin D1/PRAD1 oncogene, a key regulator of the G1 phase progression of the cell cycle has been identified as the long-sought BCL-1 oncogene in B-cell malignancies with t(11;14)(q13;q32) translocation. Recently, a novel alternative spliced cyclin D1 transcript, called transcript [b], has been identified by ourselves. The level of the variant transcript [b] was lower than that of the originally reported cyclin D1 transcript, called transcript [a], in several human non-lymphoid cancer cell lines but the endogenous cellular expression of transcript [b] products has not yet been determined. Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that the transcript [b] mRNAs are well expressed in B-lymphoid cell lines with t(11;14)(q13;q32) translocation and at much lower or undetectable levels in other cells. Western blot analysis using a human cyclin D1-specific monoclonal antibody, which can recognize and distinguish the products of transcripts [a] and [b], strongly suggested that the transcript [b] protein is indeed expressed in these B-cell lines. The present study provides the first identification of the endogenous cellular expression of the cyclin D1 transcript [b] protein and strongly suggests that this alternative form of cyclin D1 may play a significant role in the molecular pathogenesis of B-lymphoid malignancies with t(11;14)(q13;q32) translocation. Further studies are warranted to study the biological function of transcript [b] and its role in cell cycle control.

细胞周期蛋白D1/PRAD1癌基因是细胞周期G1期进展的关键调控因子，在t(11;14)（q13;q32）易位的b细胞恶性肿瘤中被确定为寻找已久的BCL-1癌基因。最近，我们发现了一种新的选择性剪接cyclin D1转录本，称为transcript [b]。在几种人类非淋巴癌细胞系中，变异转录物[b]的水平低于最初报道的cyclin D1转录物，称为转录物[a]，但转录物[b]产物的内源性细胞表达尚未确定。Northern blot分析和逆转录聚合酶链反应（RT-PCR）分析显示，转录[b] mrna在t(11;14)（q13;q32）易位的b淋巴样细胞系中表达良好，而在其他细胞中表达水平低得多或无法检测到。使用能够识别和区分转录本[a]和[b]产物的人周期蛋白d1特异性单克隆抗体进行Western blot分析，强烈提示转录本[b]蛋白确实在这些b细胞系中表达。本研究首次鉴定了细胞周期蛋白D1转录物[b]蛋白的内源性细胞表达，并强烈提示这种替代形式的细胞周期蛋白D1可能在t(11;14)（q13;q32）易位的b淋巴细胞恶性肿瘤的分子发病机制中发挥重要作用。需要进一步研究转录本的生物学功能[b]及其在细胞周期控制中的作用。