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UCSC Genome Browser Gene Interaction Graph
Gene interactions and pathways from curated databases and text-mining
Oncogene 2008, PMID: 18278068

N-myc is a novel regulator of PI3K-mediated VEGF expression in neuroblastoma.

Kang, J; Rychahou, P G; Ishola, T A; Mourot, J M; Evers, B M; Chung, D H

Angiogenesis in neuroblastoma (NB) correlates with increased expression of vascular endothelial growth factor (VEGF) and a worse clinical outcome. Other cellular markers, such as Akt activation and MYCN amplification, are also associated with poor prognosis in NB; therefore, we sought to determine the role of N-myc in the regulation of the phosphatidylinositol 3-kinase (PI3K)/Akt/VEGF pathway. PI3K inhibition, using small-molecule inhibitors or phosphatase and tensin homolog adenovirus, led to decreased levels of VEGF mRNA and/or protein by reducing phosphorylation of Akt and mammalian target of rapamycin (mTOR), and attenuating hypoxia-inducible factor 1alpha expression. Moreover, PI3K inhibition decreased levels of N-myc expression in MYCN-amplified cells. To further clarify the importance of N-myc as a target of PI3K in VEGF regulation, we inhibited N-myc expression by siRNA transfection. MYCN siRNA significantly blocked VEGF secretion, irrespective of serum conditions, in MYCN-amplified NB cells; this effect was enhanced when combined with rapamycin, an mTOR inhibitor. Interestingly, in cells with low-N-myc expression, MYCN siRNA reduction of VEGF secretion was only effective with MYCN overexpression or insulin-like growth factor-1 stimulation. Our results show that N-myc plays an important role in the PI3K-mediated VEGF regulation in NB cells. Targeting MYCN, as a novel effector of PI3K-mediated angiogenesis, has significant potential for the treatment of highly vascularized, malignant NB.

Diseases/Pathways annotated by Medline MESH: Neovascularization, Pathologic, Neuroblastoma
Document information provided by NCBI PubMed

Text Mining Data

N-myc → PI3K: " N-myc is a novel regulator of PI3K mediated VEGF expression in neuroblastoma "

VEGF → PI3K: " Our results show that N-myc plays an important role in the PI3K mediated VEGF regulation in NB cells "

Manually curated Databases

No curated data.