Insulin-like Growth Factor 1 Induces Hypoxia-inducible Factor 1-mediated Vascular Endothelial Growth Factor Expression, Which is Dependent on MAP Kinase and Phosphatidylinositol 3-Kinase Signaling…

By R. Fukuda, K. Hirota, F. Fan, Y. Jung, L. Ellis, G. Semenza. Journal of Biological Chemistry, 2002

807 citations recorded by the source corpus.

Stimulation of human colon cancer cells with insulin-like growth factor 1 (IGF-1) induces expression of theVEGF gene, encoding vascular endothelial growth factor. In this article we demonstrate that exposure of HCT116 human colon carcinoma cells to IGF-1 induces the expression of HIF-1α, the regulated subunit of hypoxia-inducible factor 1, a known transactivator of the VEGF gene. In contrast to hypoxia, which induces HIF-1α expression by inhibiting its ubiquitination and degradation, IGF-1 did not inhibit these processes, indicating an effect on HIF-1α protein synthesis. IGF-1 stimulation of HIF-1α protein and VEGF mRNA expression was inhibited by treating cells with inhibitors of phosphatidylinositol 3-kinase and MAP kinase signaling pathways. These inhibitors also blocked the IGF-1- induced phosphorylation of the translational regulatory proteins 4E-BP1, p70 S6 kinase, and eIF-4E, thus providing a mechanism for the modulation of HIF-1α protein synthesis. Forced expression of a constitutively active form of the MAP kinase kinase, MEK2, was sufficient to induce HIF-1α protein and VEGF mRNA expression. Involvement of the MAP kinase pathway represents a novel mechanism for the induction of HIF-1α protein expression in human cancer cells.

Subfields: Cancer Research, Genetics, Surgery

View Paper: https://www.semanticscholar.org/paper/698f7af5da2c11421874ee459c36dc4d85e08d3b

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Citations in the corpus

Hypoxia signalling in cancer and approaches to enforce tumour regression (2006, background): “Translation of HIF-1α has been found to be particularly sensitive to growth factors that activate mTO”
ADAPTIVE AND MALADAPTIVE CARDIORESPIRATORY RESPONSES TO CONTINUOUS AND INTERMITTENT HYPOXIA MEDIATED BY HYPOXIA-INDUCIBLE FACTORS 1 AND 2 (2012, methodology): “Analysis of IGF-I-treated colon cancer cells and insulintreated retinal epithelial cells revealed that activation of PI3K was required to induce increased HIF-1 protein levels (92, 333).”
Integration of Oxygen Signaling at the Consensus HRE (2005, background): “Because up-regulation of HIFα translation can overcome its oxygen-dependent degradation, an apparently specific increase in HIFα abundance can be observed (38, 39).”
VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model (2004, background): “Given that IGF-1 activates expression of the VEGF gene through its effect on the hypoxia inducible transcription factor, HIF-1 (ref”
Oxidation in rheumatoid arthritis (2004, background): “stabilizing and activating this key transcription factor under normoxic conditions [82–87].”
Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1α (2009, background): “HIF-1a has also been shown to be induced by numerous stimuli other than hypoxia, including insulin, insulin-like growth factors, epidermal growth factor (EGF) and heavy metals (Richard et al., 1999; Zhong et al., 2000; Fukuda et al., 2002).”
Hypoxia: Importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy (2006, neutral): “…translation of HIF-1a messenger RNA through the phosphatidylinositol 30-kinase and mitogen-activated protein kinase (MAPK) pathways (Brune & Zhou 2003, Fukuda et al. 2002, Fukuda et al. 2003, Laughner et al. 2001, Lukiw et al. 2003, Minet et al. 2001, Pichiule et al. 2004, Semenza 2001a).”