Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, LIM/42, Disciplina de Endocrinologia e Metabologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
Mol Cell Endocrinol. 2012 Mar 31;351(1):96-100. doi: 10.1016/j.mce.2011.09.042. Epub 2011 Oct 14.
The insulin-like growth factor (IGF) signaling pathway has many important roles in normal cell growth and development. Remarkably, all of the components of this system (IGFs, receptors, and binding proteins) are expressed in human fetal adrenals. Beckwith-Wiedemann syndrome, a congenital overgrowth disorder characterized by a high risk of development of childhood tumors, is also distinguished by a high incidence of adrenocortical carcinomas. This disease has been associated with structural abnormalities at the 11p15 locus, which harbors the IGF2 gene as well as the genes coding for insulin, H19, and p57kip2. Notably, rearrangements at the 11p15 locus and overexpression of IGF2 were also described in sporadic adrenocortical tumors. In addition, the IGF2 overexpression was exclusively demonstrated in adults with adrenocortical tumors as a frequent feature of the malignant state. More recent studies demonstrated that the interaction of IGF-2 with IGF receptor type 1 (IGF-1R) plays also a pivotal role in adrenocortical tumorigenesis. IGF1R expression levels were significantly higher in pediatric adrenocortical carcinomas, suggesting that IGF1R expression represents a potential prognostic marker in this group of patients. These findings indicate that the IGF system is an important pathway for autonomous growth of adrenocortical cells and potential inhibitors of this system could be a rational therapeutic target for adrenocortical tumors.
胰岛素样生长因子 (IGF) 信号通路在正常细胞生长和发育中具有许多重要作用。值得注意的是，该系统的所有组成部分（IGFs、受体和结合蛋白）均在人胎儿肾上腺中表达。Beckwith-Wiedemann 综合征是一种先天性过度生长障碍，其特征是儿童肿瘤发展的风险很高，并且还以肾上腺皮质癌的高发病率为特征。这种疾病与 11p15 基因座的结构异常有关，该基因座携带着 IGF2 基因以及编码胰岛素、H19 和 p57kip2 的基因。值得注意的是，11p15 基因座的重排和 IGF2 的过度表达也在散发性肾上腺皮质肿瘤中被描述。此外，IGF2 的过度表达仅在成年肾上腺皮质肿瘤中表现出来，是恶性状态的常见特征。最近的研究表明，IGF-2 与 IGF 受体 1（IGF-1R）的相互作用在肾上腺皮质肿瘤发生中也起着关键作用。IGF1R 在小儿肾上腺皮质癌中的表达水平显著升高，表明 IGF1R 表达可能是该组患者的潜在预后标志物。这些发现表明 IGF 系统是肾上腺皮质细胞自主生长的重要途径，该系统的潜在抑制剂可能是肾上腺皮质肿瘤的合理治疗靶点。
