<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Guerreiro AS</dc:creator>
  <dc:creator>Boller D</dc:creator>
  <dc:creator>Shalaby T</dc:creator>
  <dc:creator>Grotzer MA</dc:creator>
  <dc:creator>Arcaro A</dc:creator>
  <dc:date>2006</dc:date>
  <dc:description xmlns:ns0="xml" ns0:lang="en">The potential of the novel insulin-like growth factor receptor (IGF-IR) inhibitor NVP-AEW541 as an antiproliferative agent in human neuroblastoma was investigated. Proliferation of a panel of neuroblastoma cell lines was inhibited by NVP-AEW541 with IC(50) values ranging from 0.15 to 5 microM. Experiments using an IGF-IR neutralizing antibody confirmed that the IGF-IR was essential to support growth of neuroblastoma cell lines. The expression levels of the IGF-IR in individual neuroblastoma cell lines did not correlate with the sensitivities to NVP-AEW541, while coexpression of the IGF-IR and the insulin receptor (IR) correlated with lower sensitivity to the inhibitor in some cell lines. Intriguingly, high levels of activation of Akt/protein kinase B (PKB) and phosphorylation of the ribosomal S6 protein were observed in neuroblastoma cell lines with decreased sensitivities to NVP-AEW541. Inhibition of Akt/PKB activity restored the sensitivity of neuroblastoma cells to the IGF-IR inhibitor. Transfection of neuroblastoma cells with activated Akt or ribosomal protein S6 kinase (S6K) decreased the sensitivity of the cells to NVP-AEW541. IGF-I-stimulated proliferation of neuroblastoma cell lines was completely blocked by NVP-AEW541, or by a combination of an inhibitor of phosphoinositide 3-kinase and rapamycin. In addition to its antiproliferative effects, NVP-AEW541 sensitized neuroblastoma cells to cisplatin-induced apoptosis. Together, our data demonstrate that NVP-AEW541 in combination with Akt/PKB inhibitors or chemotherapeutic agents may represent a novel approach to target human neuroblastoma cell proliferation.</dc:description>
  <dc:identifier>https://sonar.ch/global/documents/4233</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>info:eu-repo/semantics/altIdentifier/doi/10.1002/ijc.22126</dc:relation>
  <dc:relation>info:eu-repo/semantics/altIdentifier/pmid/16988940</dc:relation>
  <dc:source>International journal of cancer. - 2006</dc:source>
  <dc:subject xmlns:ns1="xml" ns1:lang="en">Antineoplastic Agents</dc:subject>
  <dc:subject xmlns:ns2="xml" ns2:lang="en">Cell Line, Tumor</dc:subject>
  <dc:subject xmlns:ns3="xml" ns3:lang="en">Cisplatin</dc:subject>
  <dc:subject xmlns:ns4="xml" ns4:lang="en">Humans</dc:subject>
  <dc:subject xmlns:ns5="xml" ns5:lang="en">Neuroblastoma</dc:subject>
  <dc:subject xmlns:ns6="xml" ns6:lang="en">Proto-Oncogene Proteins c-akt</dc:subject>
  <dc:subject xmlns:ns7="xml" ns7:lang="en">Receptor, IGF Type 1</dc:subject>
  <dc:subject xmlns:ns8="xml" ns8:lang="en">Signal Transduction</dc:subject>
  <dc:title xmlns:ns9="xml" ns9:lang="en">Protein kinase B modulates the sensitivity of human neuroblastoma cells to insulin-like growth factor receptor inhibition.</dc:title>
  <dc:type>http://purl.org/coar/resource_type/c_6501</dc:type>
</oai_dc:dc>