Expression of hypoxia‐inducible factor 1α in tumours of patients with glioblastoma

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Abstract
Angiogenesis is a prominent feature of glioblastomas but the mechanisms involved in the control of this process are poorly understood. We have investigated the potential role of a recently described transcription factor, hypoxia‐inducible factor 1 (HIF‐1), which initiates the transcription of a number of hypoxia‐inducible genes, including those encoding vascular endothelial growth factor and its receptors. HIF‐1 protein expression was assessed by immunocytochemistry, using a monoclonal antibody to the α subunit (HIF‐1α). HIF‐1 mRNA expression was assessed by reverse transcriptase‐polymerase chain reaction (RT‐PCR) and the ribonuclease protection assay (RPA). Strong nuclear expression of HIF‐1α protein was seen in the majority of glioblastomas and anaplastic astrocytomas, particularly surrounding areas of necrosis in glioblastomas. In the majority of these tumours upregulation of HIF‐1α mRNA was also demonstrated, with a significant increase in glioblastomas compared to lower grade tumours. No correlation was found between the presence of HIF‐1α protein and immunohistochemical expression of p53 protein. These findings are in keeping with an important role of HIF‐1α in the vascularization of glioblastomas and suggest that upregulation is at least partly at a transcriptional level.

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