Insulin-like growth factor system on adrenocortical tumorigenesis

Abstract

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.