IGF2 and IGF1R in pediatric adrenocortical tumors: roles in metastasis and steroidogenesis

Autor(es):Mostrar menos -

Peixoto Lira, Regia Caroline ^[1] ; Fedatto, Paola Fernanda ^[1] ; Marco Antonio, David Santos ^[2] ; Leal, Leticia Ferro ^[1] ; Martinelli, Carlos Eduardo ^[1] ; de Castro, Margaret ^[3] ; Tucci, Silvio ^[4] ; Neder, Luciano ^[5] ; Ramalho, Leandra ^[5] ; Seidinger, Ana Luiza ^[6] ; Cardinalli, Izilda ^[6] ; Mastellaro, Maria Jose ^[6] ; Yunes, Jose Andres ^{[6, 7]} ; Brandalise, Silvia Regina ^{[6, 7]} ; Tone, Luiz Gonzaga ^[1] ; Rauber Antonini, Sonir Roberto ^[1] ; Scrideli, Carlos Alberto ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pediat, Ribeirao Preto, SP - Brazil

^[2] Fleury Grp, Dept Res & Dev, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg, Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pathol, Ribeirao Preto, SP - Brazil

^[6] State Univ Campinas UNICAMP, Boldrini Children Ctr, Campinas, SP - Brazil

^[7] State Univ Campinas UNICAMP, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Endocrine-Related Cancer; v. 23, n. 6, p. 481-493, JUN 2016.
• Citações Web of Science: 9

Resumo

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 profiles 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. Significant IGF2 overexpression was found in tumor samples when compared with non-neoplastic samples (P < 0.001), significantly 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 mu M) showed limited reduction of cell viability, suggesting that OSI-906 alone could not be a suitable therapy to abolish carcinoma cell growth. (AU)

• Processo FAPESP: 10/07020-9 - Estudos moleculares em neoplasias da criança e do adolescente: assinatura de microRNAs e estudos funcionais de genes candidatos a terapia alvo
• Beneficiário: Carlos Alberto Scrideli
• Modalidade de apoio: Auxílio à Pesquisa - Regular