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The Gene for the Axonal Cell Adhesion Molecule TAX-1 Is Amplified and Aberrantly Expressed in Malignant Gliomas

Departments of Pediatrics [D. S. R., R. T., X-X. Z., S. S., D. E. M., D. M. K., S. M. H.], Surgery [M. P. B., D. A. R., P. E. K.], Pathology [M. B.], Human Genetics [D. M. K.], and The Comprehensive Cancer Center [M. B., D. A. R., P. E. K., S. M. H.], University of Michigan Medical School, Ann Arbor, Michigan 48109, and Brain Tumor Research Center, Department of Neurological Surgery, University of California, San Francisco, California 94143-0520 [M. A. I.]

The human TAX-1 gene encodes a M_r 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.

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