The gene for the axonal cell adhesion molecule TAX-1 is amplified and aberrantly expressed in malignant gliomas

Cancer Res. 2001 Mar 1;61(5):2162-8.

Abstract

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.

MeSH terms

  • Blotting, Northern
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Adhesion Molecules, Neuronal / biosynthesis
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Cell Movement / physiology
  • Contactin 2
  • Down-Regulation
  • Gene Amplification*
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / genetics*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Immunohistochemistry
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • CNTN2 protein, human
  • Cell Adhesion Molecules, Neuronal
  • Contactin 2
  • Membrane Glycoproteins
  • RNA, Messenger