Rickman D S, Tyagi R, Zhu X X, Bobek M P, Song S, Blaivas M, Misek D E, Israel M A, Kurnit D M, Ross D A, Kish P E, Hanash S M
Department of Pediatrics, University of Michigan Medical School, Ann Arbor 48109, USA.
Cancer Res. 2001 Mar 1;61(5):2162-8.
The human TAX-1 gene encodes a Mr 135,000 glycoprotein that is transiently expressed on the surface of a subset of neurons during development and is involved in neurite outgrowth. The TAX-1 gene has been mapped to a region on chromosome 1 that has been implicated in microcephaly and the Van der Woude syndrome. Using restriction landmark genome scanning to search for amplified genes in gliomas, we found TAX-1 to be amplified in 2 high-grade gliomas among a group of 26 gliomas investigated. Real-time reverse transcription-quantitative PCR analysis detected high levels of TAX-1 mRNA in glial tumors, even in the absence of TAX-1 gene amplification. Immunohistochemical analysis revealed abundant levels of TAX-1 in neoplastic glial cells of glioblastoma multiforme tumors. Because glial tumors are highly invasive and in view of the role of TAX-1 in neurite outgrowth, we investigated the potential role of TAX-1 in glioma cell migration. Using an in vitro assay, we found that the migration of glioma tumor cells is profoundly reduced in the presence of either an anti-TAX-1 antibody or a TAX-1 antisense oligonucleotide. Our findings suggest that TAX-1 plays a role in glial tumorigenesis and may provide a potential target for therapeutic intervention.
人类TAX-1基因编码一种分子量为135,000的糖蛋白，该蛋白在发育过程中短暂表达于一部分神经元表面，并参与神经突生长。TAX-1基因已被定位到1号染色体上的一个区域，该区域与小头畸形和范德伍德综合征有关。我们使用限制性内切酶标记基因组扫描技术在胶质瘤中寻找扩增基因，发现在所研究的26例胶质瘤中有2例高级别胶质瘤中TAX-1基因发生了扩增。实时逆转录定量PCR分析检测到胶质肿瘤中TAX-1 mRNA水平很高，即使在没有TAX-1基因扩增的情况下也是如此。免疫组织化学分析显示多形性胶质母细胞瘤肿瘤的肿瘤性胶质细胞中TAX-1含量丰富。由于胶质肿瘤具有高度侵袭性，并且鉴于TAX-1在神经突生长中的作用，我们研究了TAX-1在胶质瘤细胞迁移中的潜在作用。通过体外试验，我们发现，在存在抗TAX-1抗体或TAX-1反义寡核苷酸的情况下，胶质瘤肿瘤细胞的迁移会显著减少。我们的研究结果表明，TAX-1在胶质肿瘤发生中起作用，可能为治疗干预提供一个潜在靶点。
