Almeida, M. Q., Fragoso, M. C. B. V., Lotfi, C. F. P., Santos, M. G., Nishi, M. Y., Costa, M. H. S., Lerario, A. M., Maciel, C. C., Mattos, G. E., Jorge, A. A. L., Mendonca, B. B. and Latronico, A. C. (2008) Expression of Insulin-Like Growth Factor-II and Its Receptor in Pediatric and Adult Adrenocortical Tumors. Journal of Clinical Endocrinology & Metabolism, 93 (9). pp. 3524-3531. ISSN 0021-972X

Abstract

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 +/- 0.2; 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.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... http://dx.doi.org/10.1210/jc.2008-0065
Additional Information:	Author can archive post-print (ie final draft post-refereeing); On institutional repository, PubMed Central, UK PubMed Central and PubMed Central International; Publisher's version/PDF can be used
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... http://dx.doi.org/10.1210/jc.2008-0065
Date Deposited:	13 Oct 2015 13:16
Last Modified:	13 Oct 2015 13:16
URI:	https://oak.novartis.com/id/eprint/2543