{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:13Z","timestamp":1784557213554,"version":"3.55.0"},"reference-count":60,"publisher":"Bioscientifica","issue":"6","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:p>\n                    Deregulation of the IGF system observed in human tumors indicates a role in malignant cell transformation and in tumor cell proliferation. Although overexpression of the\n                    <jats:italic>IGF2<\/jats:italic>\n                    and\n                    <jats:italic>IGF1R<\/jats:italic>\n                    genes was described in adrenocortical tumors (ACTs), few studies reported their profiles in pediatric ACTs. In this study, the\n                    <jats:italic>IGF2<\/jats:italic>\n                    and\n                    <jats:italic>IGF1R<\/jats:italic>\n                    expression was evaluated by RT-qPCR according to the patient\u2019s clinical\/pathological features in 60 pediatric ACT samples, and IGF1R protein was investigated in 45 samples by immunohistochemistry (IHC). Whole transcriptome and functional assays were conducted after IGF1R inhibition with OSI-906 in NCI-H295A cell line. Significant\n                    <jats:italic>IGF2<\/jats:italic>\n                    overexpression was found in tumor samples when compared with non-neoplastic samples (P&lt;0.001), significantly higher levels of\n                    <jats:italic>IGF1R<\/jats:italic>\n                    in patients with relapse\/metastasis (\n                    <jats:italic>P<\/jats:italic>\n                    =0.031) and moderate\/strong IGF1R immunostaining in 62.2% of ACTs, but no other relationship with patient survival and clinical\/pathological features was observed. OSI-906 treatment downregulated genes associated with MAPK activity, induced limited reduction of cell viability and increased the apoptosis rate. After 24h, the treatment also decreased the expression of genes related to the steroid biosynthetic process, the protein levels of the steroidogenic acute regulatory protein (STAR), and androgen secretion in cell medium, supporting the role of IGF1R in steroidogenesis of adrenocortical carcinoma cells. Our data showed that the\n                    <jats:italic>IGF1R<\/jats:italic>\n                    overexpression could be indicative of aggressive ACTs in children. However,\n                    <jats:italic>in vitro<\/jats:italic>\n                    treatments with high concentrations of OSI-906 (&gt;1\u03bcM) showed limited reduction of cell viability, suggesting that OSI-906 alone could not be a suitable therapy to abolish carcinoma cell growth.\n                  <\/jats:p>","DOI":"10.1530\/erc-15-0426","type":"journal-article","created":{"date-parts":[[2016,5,16]],"date-time":"2016-05-16T22:10:12Z","timestamp":1463436612000},"page":"481-493","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":23,"title":["IGF2 and IGF1R in pediatric adrenocortical tumors: roles in metastasis and steroidogenesis"],"prefix":"10.1530","volume":"23","author":[{"given":"R\u00e9gia Caroline","family":"Peixoto Lira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola Fernanda","family":"Fedatto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Santos","family":"Marco Antonio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Let\u00edcia Ferro","family":"Leal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Eduardo","family":"Martinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"de Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvio","family":"Tucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Neder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandra","family":"Ramalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Luiza","family":"Seidinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izilda","family":"Cardinalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jos\u00e9","family":"Mastellaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Andres","family":"Yunes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Regina","family":"Brandalise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Gonzaga","family":"Tone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonir Roberto","family":"Rauber Antonini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Alberto","family":"Scrideli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2016062119392447000_23.6.481.1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.4103\/0971-5851.76197","article-title":"Targeting mTOR pathway: a new concept in cancer therapy","volume":"31","author":"Advani","year":"2010","journal-title":"Indian Journal of Medical and Paediatric Oncology"},{"key":"2016062119392447000_23.6.481.2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-0052"},{"key":"2016062119392447000_23.6.481.3","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0065"},{"key":"2016062119392447000_23.6.481.4","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2953"},{"key":"2016062119392447000_23.6.481.5","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mds231"},{"key":"2016062119392447000_23.6.481.6","doi-asserted-by":"crossref","unstructured":"Boucher J Macotela Y Bezy O Mori MA Kriauciunas K Kahn CR 2010 A kinase-independent role for unoccupied insulin and IGF-1 receptors in the control of apoptosis. 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