Expression of targeting protein for Xenopus kinesin-like protein 2 is associated with progression of human malignant astrocytoma

Brain Res. 2010 Sep 17;1352:200-7. doi: 10.1016/j.brainres.2010.06.060. Epub 2010 Jun 30.

Abstract

In humans, the targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a cell cycle-associated protein, and altered TPX2 expression has been found in various malignancies. However, the contribution of TPX2 expression to astrocytoma progression is unclear. The aim of this study was to investigate TPX2 expression in human astrocytoma samples and cell lines. TPX2 protein expression was detected in the nucleus of astrocytoma tissues by immunohistochemistry and immunofluorescence staining. Real-time PCR and Western blot analysis showed that the expression levels of TPX2 were higher in high-grade astrocytoma tissues and cell lines than that in low-grade astrocytoma tissues and normal cell lines. Immunohistochemical analysis of tumor tissues from 52 patients with astrocytoma showed that TPX2 over-expression was significantly associated with decreased patient survival. In addition, down-regulation of the TPX2 gene by RNA interference inhibited proliferation of U87 cells. TPX2 gene silencing also increased early-stage apoptosis in U87 cells. Western blotting and real-time PCR showed changes in the protein and mRNA expression of Aurora A, Ran, p53, c-Myc and cyclin B1 in U87 cells that had been transfected with pSUPER/TPX2/siRNA. These data suggest that TPX2 expression is associated with the progression of malignant astrocytoma.

MeSH terms

  • Apoptosis
  • Astrocytoma / genetics*
  • Astrocytoma / mortality
  • Astrocytoma / pathology
  • Aurora Kinases
  • Brain / metabolism
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Division
  • Cell Line, Tumor
  • Cyclin B1 / genetics
  • Cyclin D1 / genetics
  • Disease Progression
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Protein-Serine-Threonine Kinases / genetics
  • Proto-Oncogene Proteins c-myc / genetics
  • Survival Rate
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Cell Cycle Proteins
  • Cyclin B1
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-myc
  • TPX2 protein, human
  • Tumor Suppressor Protein p53
  • Cyclin D1
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases