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http://purl.uniprot.org/citations/18611974http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18611974http://www.w3.org/2000/01/rdf-schema#comment"

Background

Adrenocortical tumors are heterogeneous neoplasms with incompletely understood pathogenesis. IGF-II overexpression has been consistently demonstrated in adult adrenocortical carcinomas.

Objectives

The objective of the study was to analyze expression of IGF-II and its receptor (IGF-IR) in pediatric and adult adrenocortical tumors and the effects of a selective IGF-IR kinase inhibitor (NVP-AEW541) on adrenocortical tumor cells.

Patients

Fifty-seven adrenocortical tumors (37 adenomas and 20 carcinomas) from 23 children and 34 adults were studied.

Methods

Gene expression was determined by quantitative real-time PCR. Cell proliferation and apoptosis were analyzed in NCI H295 cells and a new cell line established from a pediatric adrenocortical adenoma.

Results

IGF-II transcripts were overexpressed in both pediatric adrenocortical carcinomas and adenomas. Otherwise, IGF-II was mainly overexpressed in adult adrenocortical carcinomas (270.5 +/- 130.2 vs. 16.1 +/-13.3; P = 0.0001). IGF-IR expression was significantly higher in pediatric adrenocortical carcinomas than adenomas (9.1 +/- 3.1 vs. 2.6 +/-0.3; P = 0.0001), whereas its expression was similar in adult adrenocortical carcinomas and adenomas. IGF-IR expression was a predictor of metastases in pediatric adrenocortical tumors in univariate analysis (hazard ratio 1.84; 95% confidence interval 1.28-2.66; P = 0.01). Furthermore, NVP-AEW541 blocked cell proliferation in a dose- and time-dependent manner in both cell lines through a significant increase of apoptosis.

Conclusion

IGF-IR overexpression was a biomarker of pediatric adrenocortical carcinomas. Additionally, a selective IGF-IR kinase inhibitor had antitumor effects in adult and pediatric adrenocortical tumor cell lines, suggesting that IGF-IR inhibitors represent a promising therapy for human adrenocortical carcinoma."xsd:string
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http://purl.uniprot.org/citations/18611974http://purl.uniprot.org/core/author"Latronico A.C."xsd:string
http://purl.uniprot.org/citations/18611974http://purl.uniprot.org/core/author"Mendonca B.B."xsd:string
http://purl.uniprot.org/citations/18611974http://purl.uniprot.org/core/author"Jorge A.A."xsd:string
http://purl.uniprot.org/citations/18611974http://purl.uniprot.org/core/author"Nishi M.Y."xsd:string
http://purl.uniprot.org/citations/18611974http://purl.uniprot.org/core/author"Almeida M.Q."xsd:string
http://purl.uniprot.org/citations/18611974http://purl.uniprot.org/core/author"Fragoso M.C."xsd:string
http://purl.uniprot.org/citations/18611974http://purl.uniprot.org/core/author"Lerario A.M."xsd:string
http://purl.uniprot.org/citations/18611974http://purl.uniprot.org/core/author"Costa M.H."xsd:string
http://purl.uniprot.org/citations/18611974http://purl.uniprot.org/core/author"Santos M.G."xsd:string
http://purl.uniprot.org/citations/18611974http://purl.uniprot.org/core/author"Lotfi C.F."xsd:string
http://purl.uniprot.org/citations/18611974http://purl.uniprot.org/core/author"Maciel C.C."xsd:string
http://purl.uniprot.org/citations/18611974http://purl.uniprot.org/core/author"Mattos G.E."xsd:string
http://purl.uniprot.org/citations/18611974http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18611974http://purl.uniprot.org/core/name"J Clin Endocrinol Metab"xsd:string
http://purl.uniprot.org/citations/18611974http://purl.uniprot.org/core/pages"3524-3531"xsd:string
http://purl.uniprot.org/citations/18611974http://purl.uniprot.org/core/title"Expression of insulin-like growth factor-II and its receptor in pediatric and adult adrenocortical tumors."xsd:string
http://purl.uniprot.org/citations/18611974http://purl.uniprot.org/core/volume"93"xsd:string
http://purl.uniprot.org/citations/18611974http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/18611974
http://purl.uniprot.org/citations/18611974http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/18611974
http://purl.uniprot.org/uniprot/#_A0N9R6-mappedCitation-18611974http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18611974
http://purl.uniprot.org/uniprot/#_A0N9R7-mappedCitation-18611974http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18611974
http://purl.uniprot.org/uniprot/#_A0N9R9-mappedCitation-18611974http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18611974
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