Expression of insulin-like growth factor-II and its receptor in pediatric and adult adrenocortical tumors
Expression of insulin-like growth factor-II and its receptor in pediatric and adult adrenocortical tumors
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DOI：
10.1210/jc.2008-0065
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发表时间：
2008-09-01
影响因子：
5.8
通讯作者：
Latronico, Ana Claudia
中科院分区：
文献类型：
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作者：
Almeida, Madson Q.;Barisson Villares Fragoso, Maria Candida;Latronico, Ana Claudia
背景：肾上腺皮质肿瘤是一种异质性肿瘤，其发病机制尚不完全清楚。目的：分析儿童和成人肾上腺皮质肿瘤中IGF-II及其受体(IGF-IR)的表达，以及选择性IGF-IR激酶抑制剂(NVP-AEW541)对肾上腺肿瘤细胞的影响。对NCI H295细胞和从儿童肾上腺皮质腺瘤建立的新细胞系的细胞增殖和凋亡进行了分析。结果：IGF-II在儿童肾上腺皮质癌和腺瘤中均过表达。胰岛素样生长因子-II主要在成人肾上腺皮质癌中过表达(270.5+/-130.2 vs.16.1+/-13.3；P=0.0001)。儿童肾上腺皮质癌中IGFIR的表达显著高于腺瘤(9.1+/-3.1vs.2.6+/-0.3，P=0.0001)，而成人肾上腺皮质癌和腺瘤中IGFIR的表达相似。单因素分析显示，IGF-IR表达是儿童肾上腺皮质肿瘤转移的预测因素(危险比1.84；95%可信区间1.28-2.66；P=0.01)。此外，NVP-AEW541通过显著增加细胞凋亡率，以剂量和时间依赖的方式抑制两种细胞的增殖。结论：IGF-IR过表达是儿童肾上腺皮质癌的生物标志物。此外，一种选择性的IGF-IR激酶抑制剂在成人和儿童肾上腺皮质肿瘤细胞系中具有抗肿瘤作用，表明IGF-IR抑制剂是治疗人类肾上腺皮质癌的一种有前途的药物。
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.