Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2.
Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2.
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发表时间：
1999-08
期刊：
影响因子：
11.2
通讯作者：
D. Feldser;F. Agani;N. Iyer;Brian Pak;Gloria C. Ferreira;G. Semenza
中科院分区：
文献类型：
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作者：
D. Feldser;F. Agani;N. Iyer;Brian Pak;Gloria C. Ferreira;G. Semenza
低氧诱导因子1(HIF-1)可激活编码葡萄糖转运蛋白、糖酵解酶、血管内皮生长因子等基因的转录，以及其他与O2动态平衡和肿瘤进展相关的蛋白。HIF-1α亚基的表达和转录活性受细胞内O2浓度的调节。我们证明了胰岛素、胰岛素样生长因子(IGF)-1和IGF-2诱导HIF-1α的表达，这是编码IGF-2、IGF结合蛋白(IGFBP)-2和IGFBP-3的基因表达所必需的。这些数据提供了一种新的机制，通过这种机制，HIF-1α可能在肿瘤细胞中过表达，并有助于自分泌生长因子环。
Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding glucose transporters, glycolytic enzymes, vascular endothelial growth factor, and other proteins involved in O2 homeostasis and tumor progression. The expression and transcriptional activity of the HIF-1alpha subunit is regulated by the cellular O2 concentration. We demonstrate that insulin, insulin-like growth factor (IGF)-1, and IGF-2 induce expression of HIF-1alpha, which is required for expression of genes encoding IGF-2, IGF-binding protein (IGFBP)-2 and IGFBP-3. These data provide a novel mechanism by which HIF-1alpha overexpression may occur in tumor cells and contribute to an autocrine growth factor loop.