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

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‐1α) 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.