Kim Kyongsong, Yoshida Daizo, Teramoto Akira
Department of Neurosurgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
Endocr Pathol. 2005 Summer;16(2):115-21. doi: 10.1385/ep:16:2:115.
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.
缺氧诱导因子（HIF）-1α是缺氧适应机制中的一种转录因子。在恶性肿瘤中，HIF-1α上调血管内皮生长因子（VEGF）表达以诱导肿瘤血管生成。虽然VEGF和HIF-1α在垂体腺瘤中表达，但这些因子之间的关系仍不清楚。因此，我们使用实时逆转录聚合酶链反应（RT-PCR）和免疫组织化学检测HIF-1α和VEGF的表达，以阐明垂体腺瘤中这些因子之间的关系。使用实时RT-PCR对25例手术患者的垂体腺瘤组织中的HIF-1α mRNA和VEGF mRNA水平进行定量。一些组织也通过双重荧光免疫组织化学方法进行研究。在所检测的所有垂体腺瘤中均表达HIF-1α mRNA和蛋白。它们的表达在生长激素分泌型肿瘤中往往较高，而在促肾上腺皮质激素分泌型肿瘤中较低。VEGF mRNA和蛋白也在所有垂体腺瘤中表达。HIF-1α和VEGF mRNA的表达水平之间无显著相关性。HIF-1α和VEGF的共同表达无显著意义；仅在少数细胞中HIF-1α和VEGF共定位。我们的结果表明，在垂体腺瘤中，VEGF表达可能不太强烈地依赖于HIF-1α表达。
