Advanced search
Start date
Betweenand
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
Show less -
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]
Total Authors: 12
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. 93, n. 9, p. 3524-3531, SEP 2008.
Web of Science Citations: 108
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. (AU)

FAPESP's process: 06/00244-3 - Study of IGF-II growth factor expression and SF-1 and DAX-1 transcription factors in adrenocortical tumors in children and adults
Grantee:Madson Queiroz Almeida
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)