Expression of Hypoxia-Inducible Factor 1α and Vascular Endothelial Growth Factor in Pituitary Adenomas

Abstract

Hypoxia-inducible factor (HIF)-1alpha is a transcription factor in hypoxia adaptation mechanisms. In malignant tumors, HIF-1alpha upregulates vascular endothelial growth factor (VEGF) expression to induce tumor angiogenesis. Although VEGF and HIF-1alpha are expressed in pituitary adenomas, the relationships of these factors remain unclear. Therefore, we examined the expression of HIF-1alpha and VEGF using real-time RT-PCR and immunohistochemistry to clarify the relationship of these factors in pituitary adenomas. HIF-1alpha mRNA and VEGF mRNA levels in pituitary adenoma tissues from 25 operated patients were quantified using real-time RT-PCR. Some tissues were also studied by double fluorescent immunohistochemical methods. HIF-1alpha mRNA and protein were expressed in all pituitary adenomas examined. Their expression tended to be higher in GH-producing and lower in ACTH-producing tumors. VEGF mRNA and protein were also expressed in all pituitary adenomas. There was no significant correlation in the expression levels of HIF-1alpha and VEGF mRNA. The mutual expression of HIF-1alpha and VEGF was of no significance; in only a few cells were HIF-1alpha and VEGF co-localized. Our results suggest that in pituitary adenomas VEGF expression may not depend strongly on HIF-1alpha expression.