Expression of vascular endothelial growth factor-A and mRNA stability factor HuR in human astrocytic tumors

Neuropathology. 2008 Dec;28(6):604-11. doi: 10.1111/j.1440-1789.2008.00926.x. Epub 2008 May 21.

Abstract

High-grade astrocytic tumors, such as glioblastoma, possess rich vascular components, which are necessary for their growth. VEGF-A is considered to be the major mediator of angiogenesis in malignant neoplasms including high-grade astrocytic tumors. The upregulation of VEGF-A expression in tumor cells is induced by two mechanisms: the transcriptional activation and the post-transcriptional stabilization of VEGF-A mRNA. While the former mechanism mediated by hypoxia inducible factor-1 alpha (HIF-1alpha) has been revealed, the latter mediated by mRNA stability factor HuR remains unclear in astrocytic tumors. In the present study, we investigated the expression of VEGF-A and mRNA stability factor HuR in supratentorial astrocytic tumors of 27 adults using RT-PCR, ELISA, and immunohistochemistry. Furthermore, we studied the involvement of HuR in the upregulation of VEGF-A expression using malignant astrocytoma cell lines. In higher-grade astrocytic tumors, the level of VEGF-A and microvascular density were elevated, cytoplasmic expression of HuR, which potentially means the protection of VEGF-A mRNA from degradation by ribonucleases, appeared, and they were correlated positively. In in vitro experiments, the inhibition of the cytoplasmic translocation of HuR protein by leptomycin B (LMB) reduced the upregulation of VEGF-A expression in malignant astrocytic tumor cells under hypoxic conditions. These findings suggest that the expression of VEGF-A and cytoplasmic translocation of HuR relates to the histological grade, and that HuR is involved in the upregulation of VEGF-A expression, in human astrocytic tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inducing Agents
  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism*
  • Astrocytoma / genetics
  • Astrocytoma / metabolism*
  • Astrocytoma / pathology
  • Cytoplasm / metabolism
  • ELAV Proteins
  • ELAV-Like Protein 1
  • Enzyme-Linked Immunosorbent Assay
  • Fatty Acids, Unsaturated / pharmacology
  • Female
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • RNA Processing, Post-Transcriptional
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Supratentorial Neoplasms / genetics
  • Supratentorial Neoplasms / metabolism*
  • Supratentorial Neoplasms / pathology
  • Tumor Cells, Cultured
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*
  • Young Adult

Substances

  • Angiogenesis Inducing Agents
  • Antigens, Surface
  • ELAV Proteins
  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • Fatty Acids, Unsaturated
  • RNA-Binding Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • leptomycin B