European Journal of Biomedical and Pharmaceutical Sciences

EXPRESSION OF INSULIN-LIKE GROWTH FACTOR-II AND ITS RECEPTOR IN PEDIATRIC AND ADULT ADRENOCORTICAL TUMORS

Yoosef Hussain Alzaydey*, Saif Hussien Alzaydey, Omar Abdulaziz Al-Nasser, Norah hamad Almogri, Essa Abdulrahman Al Mutairi, Satam Essa Alhamdan, Yousef Mushahhin almutairi, Waladin Faiz Mahrus, Dina Abdulwahab Abumelha

ABSTRACT

Introduction: Adrenal cortical tumors are heterogeneous neoplasms whose pathogenesis is not fully understood. IGF-II overexpression has been consistently demonstrated in adult adrenal carcinomas. Objectives: The aim of the study was to analyze the expression of IGF-II and its receptor (IGF-IR) in pediatric and adult adrenal tumors and the effect of a selective IGF-IR kinase inhibitor (NVP-AEW541) on adrenal cortical tumor cells. patients: 57 adrenal tumors (37 adenomas and 20 carcinomas) from 23 children and 34 adults were examined. Methods: Gene expression was determined by real-time quantitative PCR. Cell proliferation and apoptosis were analyzed in NCI H295 cells and in a new cell line derived from a pediatric adrenal adenoma. Results: IGF-II transcripts were overexpressed in both adrenal cortical carcinoma and infantile adenoma. Otherwise, IGF-II was predominantly overexpressed in adult adrenal carcinomas (270.5 ±, 130.2 vs.16.1±13.3; P = 0.0001). IGF-IR expression was significantly higher in pediatric adrenocortical carcinomas than in adenomas (grades 9-12).1±3.1 versus 2.6±0.3; P=0.0001), while its expression was similar in adrenocortical carcinomas and in adult adenomas. IGF-IR expression was a predictor of adrenal tumor metastasis in children in a univariate analysis (relative risk 1.84; 95% confidence interval 1.28-2.66; p=0, 01). Furthermore, NVP-AEW541 dose- and time-dependently blocked cell proliferation in both cell lines by significantly increasing apoptosis. Conclusion: IGF-IR overexpression was a biomarker for childhood adrenal carcinoma. Furthermore, a selective IGF-IR kinase inhibitor demonstrated antitumor effects in adult and pediatric adrenal- cortical cancer cell lines, suggesting that IGF-IR inhibitors represent a promising therapy for human adrenal-cortical carcinoma.

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