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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Novel role for insulin as an autocrine growth factor for malignant brain tumour cells</title><author><name sortKey="Arcaro, Alexandre" sort="Arcaro, Alexandre" uniqKey="Arcaro A" first="Alexandre" last="Arcaro">Alexandre Arcaro</name><affiliation><nlm:aff id="A1">*Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Doepfner, Kathrin T" sort="Doepfner, Kathrin T" uniqKey="Doepfner K" first="Kathrin T." last="Doepfner">Kathrin T. Doepfner</name><affiliation><nlm:aff id="A1">*Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Boller, Danielle" sort="Boller, Danielle" uniqKey="Boller D" first="Danielle" last="Boller">Danielle Boller</name><affiliation><nlm:aff id="A1">*Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Guerreiro, Ana S" sort="Guerreiro, Ana S" uniqKey="Guerreiro A" first="Ana S." last="Guerreiro">Ana S. Guerreiro</name><affiliation><nlm:aff id="A1">*Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Shalaby, Tarek" sort="Shalaby, Tarek" uniqKey="Shalaby T" first="Tarek" last="Shalaby">Tarek Shalaby</name><affiliation><nlm:aff id="A2">†Department of Oncology, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Jackson, Shaun P" sort="Jackson, Shaun P" uniqKey="Jackson S" first="Shaun P." last="Jackson">Shaun P. Jackson</name><affiliation><nlm:aff id="A3">‡Australian Centre for Blood Diseases, Monash University, 6th Floor, Burnet Building, Alfred Medical Research and Education Precinct, Prahran, VIC 3181, Australia</nlm:aff></affiliation></author><author><name sortKey="Schoenwaelder, Simone M" sort="Schoenwaelder, Simone M" uniqKey="Schoenwaelder S" first="Simone M." last="Schoenwaelder">Simone M. Schoenwaelder</name><affiliation><nlm:aff id="A3">‡Australian Centre for Blood Diseases, Monash University, 6th Floor, Burnet Building, Alfred Medical Research and Education Precinct, Prahran, VIC 3181, Australia</nlm:aff></affiliation></author><author><name sortKey="Delattre, Olivier" sort="Delattre, Olivier" uniqKey="Delattre O" first="Olivier" last="Delattre">Olivier Delattre</name><affiliation><nlm:aff id="A4">§Institut Curie, Laboratoire de Pathologie Moléculaire des Cancers, 26 rue d'Ulm, Paris 75248, France</nlm:aff></affiliation><affiliation><nlm:aff id="A5">∥INSERM U509, Paris 75248, France</nlm:aff></affiliation></author><author><name sortKey="Grotzer, Michael A" sort="Grotzer, Michael A" uniqKey="Grotzer M" first="Michael A." last="Grotzer">Michael A. Grotzer</name><affiliation><nlm:aff id="A2">†Department of Oncology, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Fischer, Barbara" sort="Fischer, Barbara" uniqKey="Fischer B" first="Barbara" last="Fischer">Barbara Fischer</name><affiliation><nlm:aff id="A1">*Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">17506723</idno><idno type="pmc">1948991</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1948991</idno><idno type="RBID">PMC:1948991</idno><idno type="doi">10.1042/BJ20070309</idno><date when="2007">2007</date><idno type="wicri:Area/Pmc/Corpus">001372</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001372</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Novel role for insulin as an autocrine growth factor for malignant brain tumour cells</title><author><name sortKey="Arcaro, Alexandre" sort="Arcaro, Alexandre" uniqKey="Arcaro A" first="Alexandre" last="Arcaro">Alexandre Arcaro</name><affiliation><nlm:aff id="A1">*Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Doepfner, Kathrin T" sort="Doepfner, Kathrin T" uniqKey="Doepfner K" first="Kathrin T." last="Doepfner">Kathrin T. Doepfner</name><affiliation><nlm:aff id="A1">*Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Boller, Danielle" sort="Boller, Danielle" uniqKey="Boller D" first="Danielle" last="Boller">Danielle Boller</name><affiliation><nlm:aff id="A1">*Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Guerreiro, Ana S" sort="Guerreiro, Ana S" uniqKey="Guerreiro A" first="Ana S." last="Guerreiro">Ana S. Guerreiro</name><affiliation><nlm:aff id="A1">*Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Shalaby, Tarek" sort="Shalaby, Tarek" uniqKey="Shalaby T" first="Tarek" last="Shalaby">Tarek Shalaby</name><affiliation><nlm:aff id="A2">†Department of Oncology, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Jackson, Shaun P" sort="Jackson, Shaun P" uniqKey="Jackson S" first="Shaun P." last="Jackson">Shaun P. Jackson</name><affiliation><nlm:aff id="A3">‡Australian Centre for Blood Diseases, Monash University, 6th Floor, Burnet Building, Alfred Medical Research and Education Precinct, Prahran, VIC 3181, Australia</nlm:aff></affiliation></author><author><name sortKey="Schoenwaelder, Simone M" sort="Schoenwaelder, Simone M" uniqKey="Schoenwaelder S" first="Simone M." last="Schoenwaelder">Simone M. Schoenwaelder</name><affiliation><nlm:aff id="A3">‡Australian Centre for Blood Diseases, Monash University, 6th Floor, Burnet Building, Alfred Medical Research and Education Precinct, Prahran, VIC 3181, Australia</nlm:aff></affiliation></author><author><name sortKey="Delattre, Olivier" sort="Delattre, Olivier" uniqKey="Delattre O" first="Olivier" last="Delattre">Olivier Delattre</name><affiliation><nlm:aff id="A4">§Institut Curie, Laboratoire de Pathologie Moléculaire des Cancers, 26 rue d'Ulm, Paris 75248, France</nlm:aff></affiliation><affiliation><nlm:aff id="A5">∥INSERM U509, Paris 75248, France</nlm:aff></affiliation></author><author><name sortKey="Grotzer, Michael A" sort="Grotzer, Michael A" uniqKey="Grotzer M" first="Michael A." last="Grotzer">Michael A. Grotzer</name><affiliation><nlm:aff id="A2">†Department of Oncology, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Fischer, Barbara" sort="Fischer, Barbara" uniqKey="Fischer B" first="Barbara" last="Fischer">Barbara Fischer</name><affiliation><nlm:aff id="A1">*Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland</nlm:aff></affiliation></author></analytic><series><title level="j">The Biochemical Journal</title><idno type="ISSN">0264-6021</idno><idno type="eISSN">1470-8728</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>AT/RTs (atypical teratoid/rhabdoid tumours) of the CNS (central nervous system) are childhood malignancies associated with poor survival rates due to resistance to conventional treatments such as chemotherapy. We characterized a panel of human AT/RT and MRT (malignant rhabdoid tumour) cell lines for expression of RTKs (receptor tyrosine kinases) and their involvement in tumour growth and survival. When compared with normal brain tissue, AT/RT cell lines overexpressed the IR (insulin receptor) and the IGFIR (insulin-like growth factor-I receptor). Moreover, insulin was secreted by AT/RT cells grown in serum-free medium. Insulin potently activated Akt (also called protein kinase B) in AT/RT cells, as compared with other growth factors, such as epidermal growth factor. Pharmacological inhibitors, neutralizing antibodies, or RNAi (RNA interference) targeting the IR impaired the growth of AT/RT cell lines and induced apoptosis. Inhibitors of the PI3K (phosphoinositide 3-kinase)/Akt pathway also impaired basal and insulin-stimulated AT/RT cell proliferation. Experiments using RNAi and isoform-specific pharmacological inhibitors established a key role for the class I<sub>A</sub> PI3K p110α isoform in AT/RT cell growth and insulin signalling. Taken together, our results reveal a novel role for autocrine signalling by insulin and the IR in growth and survival of malignant human CNS tumour cells via the PI3K/Akt pathway.</p></div></front></TEI><pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Biochem J</journal-id><journal-id journal-id-type="pmc">bic</journal-id><journal-id journal-id-type="publisher-id">BJ</journal-id><journal-title>The Biochemical Journal</journal-title><issn pub-type="ppub">0264-6021</issn><issn pub-type="epub">1470-8728</issn><publisher><publisher-name>Portland Press Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">17506723</article-id><article-id pub-id-type="pmc">1948991</article-id><article-id pub-id-type="publisher-id">bj4060057</article-id><article-id pub-id-type="doi">10.1042/BJ20070309</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Novel role for insulin as an autocrine growth factor for malignant brain tumour cells</article-title><alt-title alt-title-type="right-running-head">Autocrine insulin signalling in central nervous system tumours</alt-title><alt-title alt-title-type="left-running-head">A. Arcaro and others</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Arcaro</surname><given-names>Alexandre</given-names></name><xref ref-type="aff" rid="A1">*</xref><xref ref-type="corresp" rid="COR1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Doepfner</surname><given-names>Kathrin T.</given-names></name><xref ref-type="aff" rid="A1">*</xref></contrib><contrib contrib-type="author"><name><surname>Boller</surname><given-names>Danielle</given-names></name><xref ref-type="aff" rid="A1">*</xref></contrib><contrib contrib-type="author"><name><surname>Guerreiro</surname><given-names>Ana S.</given-names></name><xref ref-type="aff" rid="A1">*</xref></contrib><contrib contrib-type="author"><name><surname>Shalaby</surname><given-names>Tarek</given-names></name><xref ref-type="aff" rid="A2">†</xref></contrib><contrib contrib-type="author"><name><surname>Jackson</surname><given-names>Shaun P.</given-names></name><xref ref-type="aff" rid="A3">‡</xref></contrib><contrib contrib-type="author"><name><surname>Schoenwaelder</surname><given-names>Simone M.</given-names></name><xref ref-type="aff" rid="A3">‡</xref></contrib><contrib contrib-type="author"><name><surname>Delattre</surname><given-names>Olivier</given-names></name><xref ref-type="aff" rid="A4">§</xref><xref ref-type="aff" rid="A5">∥</xref></contrib><contrib contrib-type="author"><name><surname>Grotzer</surname><given-names>Michael A.</given-names></name><xref ref-type="aff" rid="A2">†</xref></contrib><contrib contrib-type="author"><name><surname>Fischer</surname><given-names>Barbara</given-names></name><xref ref-type="aff" rid="A1">*</xref></contrib><aff id="A1">*Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland</aff><aff id="A2">†Department of Oncology, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland</aff><aff id="A3">‡Australian Centre for Blood Diseases, Monash University, 6th Floor, Burnet Building, Alfred Medical Research and Education Precinct, Prahran, VIC 3181, Australia</aff><aff id="A4">§Institut Curie, Laboratoire de Pathologie Moléculaire des Cancers, 26 rue d'Ulm, Paris 75248, France</aff><aff id="A5">∥INSERM U509, Paris 75248, France</aff></contrib-group><author-notes><corresp id="COR1"><sup>1</sup>To whom correspondence should be addressed (email <email>Alexandre.Arcaro@kispi.unizh.ch</email>).</corresp></author-notes><pub-date pub-type="epreprint"><day>16</day><month>5</month><year>2007</year></pub-date><pub-date pub-type="epub"><day>26</day><month>7</month><year>2007</year></pub-date><pub-date pub-type="ppub"><day>15</day><month>8</month><year>2007</year></pub-date><volume>406</volume><issue>Pt 1</issue><fpage>57</fpage><lpage>66</lpage><history><date date-type="received"><day>2</day><month>3</month><year>2007</year></date><date date-type="rev-recd"><day>8</day><month>5</month><year>2007</year></date><date date-type="accepted"><day>16</day><month>5</month><year>2007</year></date></history><copyright-statement>© The Authors Journal compilation © 2007 Biochemical Society</copyright-statement><copyright-year>2007</copyright-year><abstract><p>AT/RTs (atypical teratoid/rhabdoid tumours) of the CNS (central nervous system) are childhood malignancies associated with poor survival rates due to resistance to conventional treatments such as chemotherapy. We characterized a panel of human AT/RT and MRT (malignant rhabdoid tumour) cell lines for expression of RTKs (receptor tyrosine kinases) and their involvement in tumour growth and survival. When compared with normal brain tissue, AT/RT cell lines overexpressed the IR (insulin receptor) and the IGFIR (insulin-like growth factor-I receptor). Moreover, insulin was secreted by AT/RT cells grown in serum-free medium. Insulin potently activated Akt (also called protein kinase B) in AT/RT cells, as compared with other growth factors, such as epidermal growth factor. Pharmacological inhibitors, neutralizing antibodies, or RNAi (RNA interference) targeting the IR impaired the growth of AT/RT cell lines and induced apoptosis. Inhibitors of the PI3K (phosphoinositide 3-kinase)/Akt pathway also impaired basal and insulin-stimulated AT/RT cell proliferation. Experiments using RNAi and isoform-specific pharmacological inhibitors established a key role for the class I<sub>A</sub> PI3K p110α isoform in AT/RT cell growth and insulin signalling. Taken together, our results reveal a novel role for autocrine signalling by insulin and the IR in growth and survival of malignant human CNS tumour cells via the PI3K/Akt pathway.</p></abstract><kwd-group kwd-group-type="kwd"><kwd>Akt</kwd><kwd>atypical teratoid/rhabdoid tumour (AT/RT)</kwd><kwd>cell proliferation</kwd><kwd>central nervous system</kwd><kwd>insulin-like growth factor (IGF)</kwd><kwd>phosphoinositide 3-kinase (PI3K)</kwd></kwd-group><kwd-group kwd-group-type="abbr"><kwd>AT/RT, atypical teratoid/rhabdoid tumour</kwd><kwd>CNS, central nervous system</kwd><kwd>Cy3, indocarbocyanine</kwd><kwd>DMEM, Dulbecco's modified Eagle's medium</kwd><kwd>DTT, dithiothreitol</kwd><kwd>EGF, epidermal growth factor</kwd><kwd>EGFR, EGF receptor</kwd><kwd>ERK1/2, extracellular-signal-regulated kinase 1/2</kwd><kwd>FCS, foetal calf serum</kwd><kwd>GAPDH, glyceraldehyde-3-phosphate dehydrogenase</kwd><kwd>HA, haemagglutinin</kwd><kwd>hSNF5, human SNF5</kwd><kwd>IGF, insulin-like growth factor</kwd><kwd>IGFBP1, IGF-binding protein 1</kwd><kwd>IGFIR, IGF-I receptor</kwd><kwd>IR, insulin receptor</kwd><kwd>M-6-PR, mannose 6-phosphate receptor</kwd><kwd>MRT, malignant rhabdoid tumour</kwd><kwd>mTOR, mammalian target of rapamycin</kwd><kwd>MTS, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2<italic>H</italic>-tetrazolium</kwd><kwd>PDX-1, pancreatic duodenal homeobox-1</kwd><kwd>PI3K, phosphoinositide 3-kinase</kwd><kwd>PKB, protein kinase B</kwd><kwd>PTEN, phosphatase and tensin homologue deleted on chromosome 10</kwd><kwd>RNAi, RNA interference</kwd><kwd>RTKs, receptor tyrosine kinases</kwd><kwd>RT, reverse transcriptase</kwd><kwd>SCF, stem cell factor</kwd><kwd>shRNA, small-hairpin RNA</kwd><kwd>siRNAs, small interfering RNAs</kwd><kwd>S6K, S6 kinase</kwd><kwd>Tos-Lys-CH<sub>2</sub>Cl, tosyl-lysylchloromethane</kwd></kwd-group><counts><fig-count count="7"></fig-count><ref-count count="62"></ref-count><page-count count="10"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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