Igf2 And Igf1r In Pediatric Adrenocortical Tumors: Roles In Metastasis And Steroidogenesis

dc.creatorPeixoto Lira
dc.creatorRegia Caroline; Fedatto
dc.creatorPaola Fernanda; Marco Antonio
dc.creatorDavid Santos; Leal
dc.creatorLeticia Ferro; Martinelli
dc.creatorCarlos Eduardo; de Castro
dc.creatorMargaret; Tucci
dc.creatorSilvio; Neder
dc.creatorLuciano; Ramalho
dc.creatorLeandra; Seidinger
dc.creatorAna Luiza; Cardinalli
dc.creatorIzilda; Mastellaro
dc.creatorMaria Jose; Yunes
dc.creatorJose Andres; Brandalise
dc.creatorSilvia Regina; Tone
dc.creatorLuiz Gonzaga; Rauber Antonini
dc.creatorSonir Roberto; Scrideli
dc.creatorCarlos Alberto
dc.date2016
dc.datejun
dc.date2017-11-13T13:15:52Z
dc.date2017-11-13T13:15:52Z
dc.date.accessioned2018-03-29T05:53:17Z
dc.date.available2018-03-29T05:53:17Z
dc.identifierEndocrine-related Cancer. Bioscientifica Ltd, v. 23, p. 481 - 493, 2016.
dc.identifier1351-0088
dc.identifier1479-6821
dc.identifierWOS:000378753200008
dc.identifier10.1530/ERC-15-0426
dc.identifierhttp://erc.endocrinology-journals.org/content/23/6/481.long
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/327434
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1364459
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionDeregulation 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.
dc.description23
dc.description6
dc.description481
dc.description493
dc.descriptionFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Brazil [2010/07020-9]
dc.descriptionConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil
dc.descriptionFundacao de Apoio ao Ensino, Pesquisa e Assistencia do Hospital das Clinica - FMRP/USP (FAEPA), Brazil
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.languageEnglish
dc.publisherBioscientifica Ltd
dc.publisherBristol
dc.relationEndocrine-Related Cancer
dc.rightsfechado
dc.sourceWOS
dc.subjectIgf2
dc.subjectIgf1r
dc.subjectChildhood
dc.subjectAdrenocortical Tumor
dc.subjectOsi-906
dc.titleIgf2 And Igf1r In Pediatric Adrenocortical Tumors: Roles In Metastasis And Steroidogenesis
dc.typeArtículos de revistas


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