| pubmed-article:18278068 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18278068 | lifeskim:mentions | umls-concept:C0027819 | lld:lifeskim |
| pubmed-article:18278068 | lifeskim:mentions | umls-concept:C0812287 | lld:lifeskim |
| pubmed-article:18278068 | lifeskim:mentions | umls-concept:C0078058 | lld:lifeskim |
| pubmed-article:18278068 | lifeskim:mentions | umls-concept:C1256770 | lld:lifeskim |
| pubmed-article:18278068 | lifeskim:mentions | umls-concept:C0017262 | lld:lifeskim |
| pubmed-article:18278068 | lifeskim:mentions | umls-concept:C1704735 | lld:lifeskim |
| pubmed-article:18278068 | lifeskim:mentions | umls-concept:C0679622 | lld:lifeskim |
| pubmed-article:18278068 | lifeskim:mentions | umls-concept:C0205314 | lld:lifeskim |
| pubmed-article:18278068 | lifeskim:mentions | umls-concept:C2911684 | lld:lifeskim |
| pubmed-article:18278068 | lifeskim:mentions | umls-concept:C0185117 | lld:lifeskim |
| pubmed-article:18278068 | pubmed:issue | 28 | lld:pubmed |
| pubmed-article:18278068 | pubmed:dateCreated | 2008-6-26 | lld:pubmed |
| pubmed-article:18278068 | pubmed:abstractText | 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. | lld:pubmed |
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| pubmed-article:18278068 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18278068 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18278068 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:18278068 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18278068 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:18278068 | pubmed:issn | 1476-5594 | lld:pubmed |
| pubmed-article:18278068 | pubmed:author | pubmed-author:KannSS | lld:pubmed |
| pubmed-article:18278068 | pubmed:author | pubmed-author:ChungD HDH | lld:pubmed |
| pubmed-article:18278068 | pubmed:author | pubmed-author:EversB MBM | lld:pubmed |
| pubmed-article:18278068 | pubmed:author | pubmed-author:RychahouP GPG | lld:pubmed |
| pubmed-article:18278068 | pubmed:author | pubmed-author:IsholaT ATA | lld:pubmed |
| pubmed-article:18278068 | pubmed:author | pubmed-author:MourotJ MJM | lld:pubmed |
| pubmed-article:18278068 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:18278068 | pubmed:day | 26 | lld:pubmed |
| pubmed-article:18278068 | pubmed:volume | 27 | lld:pubmed |
| pubmed-article:18278068 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:18278068 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:18278068 | pubmed:pagination | 3999-4007 | lld:pubmed |
| pubmed-article:18278068 | pubmed:dateRevised | 2011-4-22 | lld:pubmed |
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