Cited by 176Adrenal and Paraganglionic TumorsGrowth Hormone and Insulin-like Growth FactorsAdrenal Hormones and Disorders

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Expression of Insulin-Like Growth Factor-II and Its Receptor in Pediatric and Adult Adrenocortical Tumors

Almeida, Madson Q., Fragoso, Maria Candida Barisson Villares, Lotfi, Claudimara Ferini Pacicco, Santos, Mariza Gerdulo, Nishi, Mirian Yumie, Costa, Marcia Helena Soares, Lerario, Antonio Marcondes, Maciel, Carolina Canton, Mattos, Gabriele Ebling, Jorge, Alexander Augusto Lima, Mendonca, Berenice B., Latronico, Ana Claudia·2008·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2008-0065

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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 +/- 0.3; 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.

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Authors: 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., & Latronico, A. C.
Affiliations: Universidade de São Paulo (BR)
Unidade de Endocrinologia do Desenvolvimento (M.Q.A., M.C.B.V.F., M.G.S., M.Y.N., M.H.S.C., A.M.L., A.A.L.J., B.B.M., A.C.L.), Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, 05403-900 São Paulo, Brazil
Corresponding author: Almeida, Madson Q.
ORCID: Almeida, Madson Q.
Fragoso, Maria Candida Barisson Villares
Lotfi, Claudimara Ferini Pacicco
Santos, Mariza Gerdulo
Nishi, Mirian Yumie
Jorge, Alexander Augusto Lima
Mendonca, Berenice B.
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2008-09-01
Volume: 93
Issue: 9
Pages: 3524-3531
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2008-0065
OpenAlex: W2095417135
Cited by: 176
References: 49
Citations by year: 2026: 4 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 10 · 2021: 6 · 2020: 13 · 2019: 6 · 2018: 11 · 2017: 5 · 2016: 10 · 2015: 12 · 2014: 17 · 2013: 7 · 2012: 17
FWCI: 16.16
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
Topics: Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords: insulin-like growth factor II, IGF-II receptor, adrenocortical tumors, pediatric adrenocortical carcinoma, adrenal adenoma, NVP-AEW541, metastasis biomarkers, cell proliferation, apoptosis, cancer therapy
MeSH terms: Adenoma, Adolescent, Adrenal Cortex Neoplasms, Adult, Aged, Carcinoma, Child, Child, Preschool, Female, Humans, Infant, Insulin-Like Growth Factor II, Male, Middle Aged, Neoplasm Metastasis, Tumor Cells, Cultured, Gene Expression Regulation, Neoplastic, Receptor, IGF Type 2

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Expression of Insulin-Like Growth Factor-II and Its Receptor in Pediatric and Adult Adrenocortical Tumors

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