Expression of insulin-like growth factor-II and its receptor in pediatric and adult adrenocortical tumors

Autor(es):Mostrar menos -

Almeida, Madson Q. ^[1] ; Barisson Villares Fragoso, Maria Candida ^[1] ; Pacicco Lotfi, Claudimara Ferini ^{[2, 3]} ; Santos, Mariza Gerdulo ^[1] ; Nishi, Mirian Yumie ^[1] ; Soares Costa, Marcia Helena ^[1] ; Lerario, Antonio Marcondes ^[1] ; Maciel, Carolina Canton ^{[2, 3]} ; Mattos, Gabriele Ebling ^{[2, 3]} ; Lima Jorge, Alexander Augusto ^[1] ; Mendonca, Berenice B. ^[1] ; Latronico, Ana Claudia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Unidade Endocrinol Desenvolvimento, BR-05403900 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Hosp Clin, Fac Med, Lab Hormonios & Genet Mol LIM42, Disciplina Endocr, BR-05403900 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Inst Ciencias Biomed, Dept Anat, BR-05403900 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. 93, n. 9, p. 3524-3531, SEP 2008.
• Citações Web of Science: 108

Resumo

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. (AU)

• Processo FAPESP: 06/00244-3 - Estudo da expressão do fator de crescimento IGF-II e dos fatores de transcrição SF-1 e DAX-1 em tumores adrenocorticais de crianças e adultos
• Beneficiário: Madson Queiroz Almeida
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto