title: Expression of insulin-like growth factor-II and its receptor in pediatric and adult adrenocortical tumors.
abstract: BACKGROUND
  Adrenocortical tumors are heterogeneous neoplasms with incompletely understood pathogenesis. IGF-II overexpression has been consistently demonstrated in adult adrenocortical carcinomas.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular/LIM-42 da Disciplina de Endocrinologia do Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo, SP, Brasil. madsonalmeida@gmail.com
authors.forename: Madson Q
authors.initials: MQ
authors.lastname: Almeida
authors.forename: Maria Candida Barisson Villares
authors.initials: MC
authors.lastname: Fragoso
authors.forename: Claudimara Ferini Pacicco
authors.initials: CF
authors.lastname: Lotfi
authors.forename: Mariza Gerdulo
authors.initials: MG
authors.lastname: Santos
authors.forename: Mirian Yumie
authors.initials: MY
authors.lastname: Nishi
authors.forename: Marcia Helena Soares
authors.initials: MH
authors.lastname: Costa
authors.forename: Antonio Marcondes
authors.initials: AM
authors.lastname: Lerario
authors.forename: Carolina Canton
authors.initials: CC
authors.lastname: Maciel
authors.forename: Gabriele Ebling
authors.initials: GE
authors.lastname: Mattos
authors.forename: Alexander Augusto Lima
authors.initials: AA
authors.lastname: Jorge
authors.forename: Berenice B
authors.initials: BB
authors.lastname: Mendonca
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Latronico
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017527:Receptor, IGF Type 2 / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II