Wei Kuo Chen, Berger Mitchel S, Sehgal Anil
Chang Gung Memorial Hospital, 1st Division of Neurosurgery, Taoyuan, Taiwan.
Anticancer Res. 2002 Mar-Apr;22(2A):649-57.
Using the technique of differential hybridization of a human fetal brain library, we have identified a novel gene, brain 2 (BR-2). This gene is expressed in normal brain but has low or no expression in human oligodendrogliomas and other brain tumor samples. We have cloned and sequenced the full-length cDNA corresponding to this gene. A data base search for the nucleotide sequence homology was performed for BR-2. BR-2 sequence showed strong homolog to a human genomic clone from chromosome 2. Moderate sequence homology was observed between BR-2 and an EST from a human placenta library. Multiple tissue dot blot analysis indicated that the BR-2 gene is expressed in a number of tissues including brain, heart, lung, placenta, lymph node, trachea and kidney. The BR-2 gene is also expressed in fetal heart, spleen and lung tissue. An extremely high level of BR-2 expression is observed in the left atrium of the heart. Low or no expression of BR-2 expression is observed in sixteen human cancer cell lines. RT-PCR analysis indicated that the BR-2 gene is expressed at high levels in two of the five normal brain tissue samples analyzed. Except for low expression in one oligodendroglioma, no expression of BR-1 gene was observed in eight anaplastic astrocytomas and glioblastoma multiforme tissue samples. Four of nine glioblastoma tumor cell lines did show a low level of BR-2 expression. On the basis of its expression and sequence, we conclude that BR-2 is a novel gene with unique expression properties in human brain tumors.
利用人胎儿脑文库的差异杂交技术，我们鉴定出一个新基因——脑2（BR-2）。该基因在正常脑中表达，但在人少突胶质细胞瘤和其他脑肿瘤样本中表达低或无表达。我们已克隆并测序了与该基因对应的全长cDNA。对BR-2进行了核苷酸序列同源性的数据库搜索。BR-2序列与来自2号染色体的一个人类基因组克隆显示出高度同源性。在BR-2与来自人胎盘文库的一个EST之间观察到中度序列同源性。多组织点杂交分析表明，BR-2基因在包括脑、心脏、肺、胎盘、淋巴结、气管和肾脏在内的多种组织中表达。BR-2基因在胎儿心脏、脾脏和肺组织中也有表达。在心脏左心房中观察到BR-2的极高表达水平。在16种人类癌细胞系中观察到BR-2表达低或无表达。RT-PCR分析表明，在分析的5个正常脑组织样本中有2个样本中BR-2基因高水平表达。除了在一个少突胶质细胞瘤中有低表达外，在8个间变性星形细胞瘤和多形性胶质母细胞瘤组织样本中未观察到BR-1基因的表达。9个胶质母细胞瘤肿瘤细胞系中有4个确实显示出低水平的BR-2表达。基于其表达和序列，我们得出结论，BR-2是一个在人类脑肿瘤中具有独特表达特性的新基因。
