Expression of hypoxia-inducible factor 1alpha and vascular endothelial growth factor in pituitary adenomas.
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.
Kim
Kyongsong
K
Department of Neurosurgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan. kyongson@nms.ac.jp
Yoshida
Daizo
D
Teramoto
Akira
A
D000236:Adenoma / Q000098:blood supply / Q000378:metabolism*; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000098:blood supply / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A