DOI: 10.1530/ERC-15-0426 http://erc.endocrinology-journals.org © 2016 Society for Endocrinology Printed in Great Britain Published by Bioscientifca Ltd. Endocrine-Related Cancer Abstract 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 IGF2 and IGF1R genes was described in adrenocortical tumors (ACTs), few studies reported their profles in pediatric ACTs. In this study, the IGF2 and IGF1R expression was evaluated by RT-qPCR according to the patient’s 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. Signifcant IGF2 overexpression was found in tumor samples when compared with non-neoplastic samples (P < 0.001), signifcantly higher levels of IGF1R in patients with relapse/metastasis (P = 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 24 h, 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 IGF1R overexpression could be indicative of aggressive ACTs in children. However, in vitro treatments with high concentrations of OSI-906 (>1 μM) showed limited reduction of cell viability, suggesting that OSI-906 alone could not be a suitable therapy to abolish carcinoma cell growth. 23:6 Research R C P Lira et al. IGF1R in pediatric adrenocortical tumor IGF2 and IGF1R in pediatric adrenocortical tumors: roles in metastasis and steroidogenesis Régia Caroline Peixoto Lira 1 , Paola Fernanda Fedatto 1 , David Santos Marco Antonio 2 , Letícia Ferro Leal 1 , Carlos Eduardo Martinelli 1 , Margaret de Castro 3 , Silvio Tucci 4 , Luciano Neder 5 , Leandra Ramalho 5 , Ana Luiza Seidinger 6 , Izilda Cardinalli 6 , Maria José Mastellaro 6 , José Andres Yunes 6,7 , Silvia Regina Brandalise 6,7 , Luiz Gonzaga Tone 1 , Sonir Roberto Rauber Antonini 1 and Carlos Alberto Scrideli 1 1 Department of Pediatrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, São Paulo, Brazil 2 Department of Research and Development, Fleury Group, Sao Paulo, São Paulo, Brazil 3 Department of Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, São Paulo, Brazil 4 Department of Surgery, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, São Paulo, Brazil 5 Department of Pathology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, São Paulo, Brazil 6 Boldrini Children Center, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil 7 State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil 481–493 Correspondence should be addressed to Carlos Alberto Scrideli Email scrideli@fmrp.usp.br Key Words f IGF2 f IGF1R f childhood f adrenocortical tumor f OSI-906 Endocrine-Related Cancer (2016) 23, 481–493 Downloaded from Bioscientifica.com at 11/25/2018 08:41:26AM via free access